Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000015613.78314.9E
M. Fujii, A. Wada, T. Tsutamoto, M. Ohnishi, T. Isono, M. Kinoshita
Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P <0.01), prolonged the time constant of relaxation (P <0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca2+-ATPase mRNA (P <0.05). FR173657 also upregulated collagen type I and III mRNA (P <0.05) and increased the total amount of cardiac collagen deposits (P <0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca2+ handling and suppression of collagen accumulation.
{"title":"Bradykinin Improves Left Ventricular Diastolic Function Under Long-Term Angiotensin-Converting Enzyme Inhibition in Heart Failure","authors":"M. Fujii, A. Wada, T. Tsutamoto, M. Ohnishi, T. Isono, M. Kinoshita","doi":"10.1161/01.HYP.0000015613.78314.9E","DOIUrl":"https://doi.org/10.1161/01.HYP.0000015613.78314.9E","url":null,"abstract":"Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P <0.01), prolonged the time constant of relaxation (P <0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca2+-ATPase mRNA (P <0.05). FR173657 also upregulated collagen type I and III mRNA (P <0.05) and increased the total amount of cardiac collagen deposits (P <0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca2+ handling and suppression of collagen accumulation.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"46 1","pages":"952-957"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88152700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000017553.67732.E1
S. Yoshimura, R. Morishita, K. Hayashi, J. Kokuzawa, M. Aoki, Kunio Matsumoto, Toshikazu Nakamura, T. Ogihara, N. Sakai, Y. Kaneda
Although cerebral hypoperfusion caused by cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. Recently, a novel therapeutic strategy for ischemic disease using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. Therapeutic angiogenesis might be useful for the treatment of cerebral occlusive disease. Hepatocyte growth factor (HGF) is a potent angiogenic factor, in addition to vascular endothelial growth factor (VEGF), whereas in the nervous system HGF also acts as neurotrophic factor. Therefore, we hypothesized that gene transfer of these angiogenic growth factors could induce angiogenesis, thus providing an effective therapy for cerebral hypoperfusion or stroke. In this study, we employed a highly efficient gene transfer method, the viral envelop (Hemagglutinating Virus of Japan [HVJ]-liposome) method, because we previously documented that &bgr;-galactosidase gene could be transfected into the brain by the HVJ-liposome method. Indeed, we confirmed wide distribution of transgene expression using &bgr;-galactosidase via injection into the subarachnoid space. Of importance, transfection of HGF or VEGF gene into the subarachnoid space 7 days before occlusion induced angiogenesis on the brain surface as assessed by alkaline phosphatase staining (P <0.01). In addition, significant improvement of cerebral blood flow (CBF) was observed by laser Doppler imaging (LDI) 7 days after occlusion (P <0.01). Unexpectedly, transfection of HGF or VEGF gene into the subarachnoid space immediately after occlusion of the bilateral carotid arteries also induced angiogenesis on the brain surface and had a significant protective effect on the impairment of CBF by carotid occlusion (P <0.01). Interestingly, coinjection of recombinant HGF with HGF gene transfer revealed a further increase in CBF (P <0.01). Here, we demonstrated successful therapeutic angiogenesis using HGF or VEGF gene transfer into the subarachnoid space to improve cerebral hypoperfusion, thus providing a new therapeutic strategy for cerebral ischemic disease.
{"title":"Gene Transfer of Hepatocyte Growth Factor to Subarachnoid Space in Cerebral Hypoperfusion Model","authors":"S. Yoshimura, R. Morishita, K. Hayashi, J. Kokuzawa, M. Aoki, Kunio Matsumoto, Toshikazu Nakamura, T. Ogihara, N. Sakai, Y. Kaneda","doi":"10.1161/01.HYP.0000017553.67732.E1","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017553.67732.E1","url":null,"abstract":"Although cerebral hypoperfusion caused by cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. Recently, a novel therapeutic strategy for ischemic disease using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. Therapeutic angiogenesis might be useful for the treatment of cerebral occlusive disease. Hepatocyte growth factor (HGF) is a potent angiogenic factor, in addition to vascular endothelial growth factor (VEGF), whereas in the nervous system HGF also acts as neurotrophic factor. Therefore, we hypothesized that gene transfer of these angiogenic growth factors could induce angiogenesis, thus providing an effective therapy for cerebral hypoperfusion or stroke. In this study, we employed a highly efficient gene transfer method, the viral envelop (Hemagglutinating Virus of Japan [HVJ]-liposome) method, because we previously documented that &bgr;-galactosidase gene could be transfected into the brain by the HVJ-liposome method. Indeed, we confirmed wide distribution of transgene expression using &bgr;-galactosidase via injection into the subarachnoid space. Of importance, transfection of HGF or VEGF gene into the subarachnoid space 7 days before occlusion induced angiogenesis on the brain surface as assessed by alkaline phosphatase staining (P <0.01). In addition, significant improvement of cerebral blood flow (CBF) was observed by laser Doppler imaging (LDI) 7 days after occlusion (P <0.01). Unexpectedly, transfection of HGF or VEGF gene into the subarachnoid space immediately after occlusion of the bilateral carotid arteries also induced angiogenesis on the brain surface and had a significant protective effect on the impairment of CBF by carotid occlusion (P <0.01). Interestingly, coinjection of recombinant HGF with HGF gene transfer revealed a further increase in CBF (P <0.01). Here, we demonstrated successful therapeutic angiogenesis using HGF or VEGF gene transfer into the subarachnoid space to improve cerebral hypoperfusion, thus providing a new therapeutic strategy for cerebral ischemic disease.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"20 1","pages":"1028-1034"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88390990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000016177.20565.A0
P. Lantelme, A. Rohrwasser, B. Gociman, E. Hillas, T. Cheng, Gray Petty, Jennifer Thomas, S. Xiao, T. Ishigami, Tracy Herrmann, D. Terreros, K. Ward, J. Lalouel
Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains, the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly higher urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion.
{"title":"Effects of Dietary Sodium and Genetic Background on Angiotensinogen and Renin in Mouse","authors":"P. Lantelme, A. Rohrwasser, B. Gociman, E. Hillas, T. Cheng, Gray Petty, Jennifer Thomas, S. Xiao, T. Ishigami, Tracy Herrmann, D. Terreros, K. Ward, J. Lalouel","doi":"10.1161/01.HYP.0000016177.20565.A0","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016177.20565.A0","url":null,"abstract":"Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains, the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly higher urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"124 1 1","pages":"1007-1014"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85202500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000016920.96457.7C
T. S. Manning, B. Shykoff, J. Izzo
The present study assessed (1) the impact of the measurement site (lower versus upper extremity) on the corresponding compliance variables and (2) the overall reliability of diastolic pulse contour (Windkessel-derived) analysis in normal and hypertensive subjects. Arterial tonograms were recorded in the supine position from the radial and posterior tibial arteries in 20 normotensive (116±12/68±8 mm Hg) and 27 essential hypertensive subjects (160±16/94±14 mm Hg). Ensemble-averaged data for each subject were fitted to a first-order lumped-parameter model (basic Windkessel) to compute whole-body arterial compliance (CA) and to a third-order lumped-parameter model (modified Windkessel) to compute proximal compliance (C1) and distal compliance (C2). Despite high-fidelity waveforms in each subject, the first-order Windkessel model did not yield interpretable (positive) values for CA in 50% of normotensives and 41% of hypertensives, whereas the third-order model failed to yield interpretable C1 or C2 results in 15% of normotensives and 41% of hypertensives. No between-site correlations were found for the first-order time constant, 2 of the 3 third-order model curve-fitting constants, or CA, C1, or C2 (P >0.50). Mean values for all 3 compliance variables were higher for the leg than the arm (P <0.05 each). We conclude that differences in Windkessel-derived compliance values in the arm and leg invalidate whole-body model assumptions and suggest a strong influence of regional circulatory properties. The validity and utility of Windkessel-derived variables is further diminished by the absence of between-site correlations and the common occurrence of uninterpretable values in hypertensive subjects.
本研究评估了(1)测量部位(下肢与上肢)对相应顺应性变量的影响，(2)正常和高血压受试者舒张期脉搏轮廓(windkesel衍生)分析的总体可靠性。记录20例正常血压患者(116±12/68±8 mm Hg)和27例原发性高血压患者(160±16/94±14 mm Hg)仰卧位时桡动脉和胫后动脉的动脉张力图。每个受试者的整体平均数据拟合到一阶集总参数模型(基本Windkessel)以计算全身动脉顺应性(CA)，并拟合到三阶集总参数模型(改进的Windkessel)以计算近端顺应性(C1)和远端顺应性(C2)。尽管每个受试者的波形保真度很高，但一阶Windkessel模型在50%的正常血压患者和41%的高血压患者中不能产生可解释的(阳性)CA值，而三阶模型在15%的正常血压患者和41%的高血压患者中不能产生可解释的C1或C2结果。一阶时间常数、3个三阶模型曲线拟合常数中的2个或CA、C1或C2均未发现位点间相关性(P >0.50)。3个顺应性变量的平均值在腿部高于手臂(P <0.05)。我们的结论是，windkessel衍生的手臂和腿部顺应性值的差异使全身模型假设无效，并表明区域循环特性的强烈影响。windkessel衍生变量的有效性和效用由于缺乏位点间相关性和高血压受试者中常见的不可解释值而进一步降低。
{"title":"Validity and Reliability of Diastolic Pulse Contour Analysis (Windkessel Model) in Humans","authors":"T. S. Manning, B. Shykoff, J. Izzo","doi":"10.1161/01.HYP.0000016920.96457.7C","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016920.96457.7C","url":null,"abstract":"The present study assessed (1) the impact of the measurement site (lower versus upper extremity) on the corresponding compliance variables and (2) the overall reliability of diastolic pulse contour (Windkessel-derived) analysis in normal and hypertensive subjects. Arterial tonograms were recorded in the supine position from the radial and posterior tibial arteries in 20 normotensive (116±12/68±8 mm Hg) and 27 essential hypertensive subjects (160±16/94±14 mm Hg). Ensemble-averaged data for each subject were fitted to a first-order lumped-parameter model (basic Windkessel) to compute whole-body arterial compliance (CA) and to a third-order lumped-parameter model (modified Windkessel) to compute proximal compliance (C1) and distal compliance (C2). Despite high-fidelity waveforms in each subject, the first-order Windkessel model did not yield interpretable (positive) values for CA in 50% of normotensives and 41% of hypertensives, whereas the third-order model failed to yield interpretable C1 or C2 results in 15% of normotensives and 41% of hypertensives. No between-site correlations were found for the first-order time constant, 2 of the 3 third-order model curve-fitting constants, or CA, C1, or C2 (P >0.50). Mean values for all 3 compliance variables were higher for the leg than the arm (P <0.05 each). We conclude that differences in Windkessel-derived compliance values in the arm and leg invalidate whole-body model assumptions and suggest a strong influence of regional circulatory properties. The validity and utility of Windkessel-derived variables is further diminished by the absence of between-site correlations and the common occurrence of uninterpretable values in hypertensive subjects.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"53 1","pages":"963-968"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90927967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000016178.80811.D9
J. Stamler, Kiang Liu, K. Ruth, J. Pryer, P. Greenland
Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro- and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change.
{"title":"Eight-Year Blood Pressure Change in Middle-Aged Men: Relationship to Multiple Nutrients","authors":"J. Stamler, Kiang Liu, K. Ruth, J. Pryer, P. Greenland","doi":"10.1161/01.HYP.0000016178.80811.D9","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016178.80811.D9","url":null,"abstract":"Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro- and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"93 1","pages":"1000-1006"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79016573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000016921.50185.7B
Caroline Rhéaume, P. Waib, Y. Lacourciére, A. Nadeau, J. Cléroux
Physical exercise increases insulin sensitivity in conditions associated with insulin resistance, such as obesity and diabetes, but little is known in this regard in hypertension. Whether postexercise changes in hemodynamics and/or changes in insulin-induced vasodilatation could contribute to a postexercise increase in insulin sensitivity in hypertensive subjects is unknown. We investigated the effects of acute physical exercise on insulin sensitivity in 10 hypertensive and 10 normotensive subjects during a control evaluation (CTRL), during lower body negative pressure (LBNP), after 30 minutes of mild bicycle exercise (POSTEX), and during LBNP after exercise (POSTEX+LBNP). Insulin-induced vasodilatation was assessed from peak forearm blood flow during the intravenous glucose tolerance test. Cardiac output (4.9±0.3 versus 5.3±0.4 L/min, mean±SEM) and insulin sensitivity (the glucose disappearance rate over insulin area under the curve: 0.91±0.07 versus 1.38±0.25 min−1/[pmol · L−1] · minute) were lower (both P <0.05) in hypertensive than in normotensive subjects, respectively. Cardiac output decreased during LBNP, increased during POSTEX, and was similar to control during POSTEX+LBNP in both groups. Insulin sensitivity was unchanged during LBNP, increased during POSTEX, and remained elevated during POSTEX+LBNP in hypertensive subjects, whereas it remained unchanged in normotensives. Peak forearm blood flow was significantly lower in hypertensive than in normotensive subjects, despite higher insulin levels in hypertensives, and was not modified by LBNP or exercise. In conclusion, insulin sensitivity increases after exercise in hypertensive subjects, and the increase in cardiac output does not contribute to this effect. Endogenous insulin-induced vasodilatation is reduced in hypertensive subjects, and this insulin action is not affected by physical exercise.
在与胰岛素抵抗相关的情况下，如肥胖和糖尿病，体育锻炼会增加胰岛素敏感性，但在高血压方面却知之甚少。运动后血液动力学的改变和/或胰岛素诱导的血管舒张的改变是否会导致高血压患者运动后胰岛素敏感性的增加尚不清楚。我们研究了10名高血压和10名正常受试者在对照评估(CTRL)、下体负压(LBNP)、30分钟轻度自行车运动(POSTEX)和运动后LBNP (POSTEX+LBNP)期间急性体育锻炼对胰岛素敏感性的影响。在静脉葡萄糖耐量试验中，通过前臂血流量峰值来评估胰岛素诱导的血管舒张。高血压组心输出量(4.9±0.3 vs 5.3±0.4 L/min，平均值±SEM)和胰岛素敏感性(胰岛素曲线下葡萄糖消失率:0.91±0.07 vs 1.38±0.25 min−1/[pmol·L−1]·min)均低于正常组(P <0.05)。两组在LBNP期间心输出量下降，在POSTEX期间增加，并且在POSTEX+LBNP期间与对照组相似。高血压患者的胰岛素敏感性在LBNP期间保持不变，在POSTEX期间增加，并且在POSTEX+LBNP期间保持升高，而在血压正常者中保持不变。尽管高血压患者的胰岛素水平较高，但高血压患者的前臂血流量峰值明显低于正常受试者，并且不受LBNP或运动的影响。综上所述，高血压患者运动后胰岛素敏感性增加，心输出量的增加与此无关。内源性胰岛素诱导的血管舒张在高血压患者中降低，并且这种胰岛素作用不受体育锻炼的影响。
{"title":"Effects of Mild Exercise on Insulin Sensitivity in Hypertensive Subjects","authors":"Caroline Rhéaume, P. Waib, Y. Lacourciére, A. Nadeau, J. Cléroux","doi":"10.1161/01.HYP.0000016921.50185.7B","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016921.50185.7B","url":null,"abstract":"Physical exercise increases insulin sensitivity in conditions associated with insulin resistance, such as obesity and diabetes, but little is known in this regard in hypertension. Whether postexercise changes in hemodynamics and/or changes in insulin-induced vasodilatation could contribute to a postexercise increase in insulin sensitivity in hypertensive subjects is unknown. We investigated the effects of acute physical exercise on insulin sensitivity in 10 hypertensive and 10 normotensive subjects during a control evaluation (CTRL), during lower body negative pressure (LBNP), after 30 minutes of mild bicycle exercise (POSTEX), and during LBNP after exercise (POSTEX+LBNP). Insulin-induced vasodilatation was assessed from peak forearm blood flow during the intravenous glucose tolerance test. Cardiac output (4.9±0.3 versus 5.3±0.4 L/min, mean±SEM) and insulin sensitivity (the glucose disappearance rate over insulin area under the curve: 0.91±0.07 versus 1.38±0.25 min−1/[pmol · L−1] · minute) were lower (both P <0.05) in hypertensive than in normotensive subjects, respectively. Cardiac output decreased during LBNP, increased during POSTEX, and was similar to control during POSTEX+LBNP in both groups. Insulin sensitivity was unchanged during LBNP, increased during POSTEX, and remained elevated during POSTEX+LBNP in hypertensive subjects, whereas it remained unchanged in normotensives. Peak forearm blood flow was significantly lower in hypertensive than in normotensive subjects, despite higher insulin levels in hypertensives, and was not modified by LBNP or exercise. In conclusion, insulin sensitivity increases after exercise in hypertensive subjects, and the increase in cardiac output does not contribute to this effect. Endogenous insulin-induced vasodilatation is reduced in hypertensive subjects, and this insulin action is not affected by physical exercise.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"23 1","pages":"989-995"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72923664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000017552.91014.2A
O. Melander, E. Frandsen, L. Groop, U. Hulthén
The aim of the present study was to investigate whether plasma concentration of proANP1–30, the N-terminal fragment of the atrial natriuretic peptide prohormone, or 24-hour urinary excretion of urodilatin reflects the degree of salt sensitivity in hypertension-prone individuals. Plasma concentration of proANP1–30 and urinary urodilatin excretion were determined at baseline, after 1 week on a low-salt diet (10 mmol/d) and after another week on a high-salt diet (240 mmol/d) in 30 healthy subjects with heredity for hypertension. Salt sensitivity was defined as the difference between mean arterial blood pressure after the high-salt diet and the mean arterial blood pressure after the low-salt diet. High- versus low-salt intake increased proANP1–30 (668±330 versus 358±150 pmol/L;P <0.00001) and urodilatin (18.7±5.2 versus 16.0±8.3 pmol/24 h;P <0.05). ProANP1–30 correlated with salt sensitivity at baseline (r =0.76, P <0.000001), after the low- (r =0.80, P <0.0000001) and high-salt diets (r =0.85, P <0.00000001). The increase in proANP1–30 induced by changing from the low- to the high-salt diet was also directly related to salt sensitivity (r =0.78, P <0.000001). ProANP1–30 was not related to urinary sodium excretion. Neither urodilatin nor the sodium-induced change in urodilatin correlated with salt sensitivity. However, urodilatin was related to the urinary sodium excretion at baseline (r =0.58, P <0.01) and after the high-salt diet (r =0.62, P <0.001). In conclusion, the close correlations between proANP1–30 and salt sensitivity suggest that proANP1–30 may serve as a marker for salt sensitivity and could be useful in identifying subjects who would benefit from dietary salt restriction to prevent development of hypertension.
本研究的目的是探讨血浆anp1 - 30(心房钠素肽原激素n端片段)或尿舒张素24小时排泄量是否反映高血压易感人群的盐敏感程度。在30例具有高血压遗传的健康受试者中，分别在基线、低盐饮食(10 mmol/d) 1周和高盐饮食(240 mmol/d) 1周后测定血浆proANP1-30浓度和尿舒张素排泄量。盐敏感性定义为高盐饮食后平均动脉血压与低盐饮食后平均动脉血压之差。高盐摄入比低盐摄入增加proANP1-30(668±330比358±150 pmol/L, P <0.00001)和尿舒张素(18.7±5.2比16.0±8.3 pmol/24 h, P <0.05)。在低盐饮食(r =0.80, P <0.0000001)和高盐饮食(r =0.85, P <0.00000001)之后，ProANP1-30在基线时与盐敏感性相关(r =0.76, P <0.000001)。由低盐日粮转为高盐日粮诱导的proANP1-30升高也与盐敏感性直接相关(r =0.78, P <0.000001)。ProANP1-30与尿钠排泄无关。尿舒张素和钠诱导的尿舒张素变化均与盐敏感性无关。然而，尿舒张素与基线时(r =0.58, P <0.01)和高盐饮食后的尿钠排泄相关(r =0.62, P <0.001)。综上所述，proANP1-30与盐敏感性之间的密切相关表明proANP1-30可能作为盐敏感性的标记物，并可用于确定哪些受试者将受益于饮食盐限制以预防高血压的发生。
{"title":"Plasma ProANP1–30 Reflects Salt Sensitivity in Subjects With Heredity for Hypertension","authors":"O. Melander, E. Frandsen, L. Groop, U. Hulthén","doi":"10.1161/01.HYP.0000017552.91014.2A","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017552.91014.2A","url":null,"abstract":"The aim of the present study was to investigate whether plasma concentration of proANP1–30, the N-terminal fragment of the atrial natriuretic peptide prohormone, or 24-hour urinary excretion of urodilatin reflects the degree of salt sensitivity in hypertension-prone individuals. Plasma concentration of proANP1–30 and urinary urodilatin excretion were determined at baseline, after 1 week on a low-salt diet (10 mmol/d) and after another week on a high-salt diet (240 mmol/d) in 30 healthy subjects with heredity for hypertension. Salt sensitivity was defined as the difference between mean arterial blood pressure after the high-salt diet and the mean arterial blood pressure after the low-salt diet. High- versus low-salt intake increased proANP1–30 (668±330 versus 358±150 pmol/L;P <0.00001) and urodilatin (18.7±5.2 versus 16.0±8.3 pmol/24 h;P <0.05). ProANP1–30 correlated with salt sensitivity at baseline (r =0.76, P <0.000001), after the low- (r =0.80, P <0.0000001) and high-salt diets (r =0.85, P <0.00000001). The increase in proANP1–30 induced by changing from the low- to the high-salt diet was also directly related to salt sensitivity (r =0.78, P <0.000001). ProANP1–30 was not related to urinary sodium excretion. Neither urodilatin nor the sodium-induced change in urodilatin correlated with salt sensitivity. However, urodilatin was related to the urinary sodium excretion at baseline (r =0.58, P <0.01) and after the high-salt diet (r =0.62, P <0.001). In conclusion, the close correlations between proANP1–30 and salt sensitivity suggest that proANP1–30 may serve as a marker for salt sensitivity and could be useful in identifying subjects who would benefit from dietary salt restriction to prevent development of hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"97 1","pages":"996-999"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83089156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000017283.67962.02
H. Jackman, M. Massad, M. Sekosan, F. Tan, V. Brovkovych, B. Marcic, E. G. Erdös
Human heart tissue enzymes cleave angiotensin (Ang) I to release Ang 1-9, Ang II, or Ang 1-7. In atrial homogenate preparations, cathepsin A (deamidase) is responsible for 65% of the liberated Ang 1-9. Ang 1-7 was released (88% to 100%) by a metallopeptidase, as established with peptidase inhibitors. Ang II was liberated to about equal degrees by ACE and chymase-type enzymes. Cathepsin A’s presence in heart tissue was also proven because it deamidated enkephalinamide substrate by immunoprecipitation of cathepsin A with antiserum to human recombinant enzyme and by immunohistochemistry. In immunohistochemistry, cathepsin A was detected in myocytes of atrial tissue. The products of Ang I cleavage, Ang 1-9 and Ang 1-7, potentiated the effect of an ACE-resistant bradykinin analog and enhanced kinin effect on the B2 receptor in Chinese hamster ovary cells transfected to express human ACE and B2 (CHO/AB), and in human pulmonary arterial endothelial cells. Ang 1-9 and 1-7 augmented arachidonic acid and nitric oxide (NO) release by kinin. Direct assay of NO liberation by bradykinin from endothelial cells was potentiated at 10 nmol/L concentration, 2.4-fold (Ang 1-9) and 2.1-fold (Ang 1-7); in higher concentrations, Ang 1-9 was significantly more active than Ang 1-7. Both peptides had traces of activity in the absence of bradykinin. Ang 1-9 and Ang 1-7 potentiated bradykinin action on the B2 receptor by raising arachidonic acid and NO release at much lower concentrations than their 50% inhibition concentrations (IC50s) with ACE. They probably induce conformational changes in the ACE/B2 receptor complex via interaction with ACE.
{"title":"Angiotensin 1-9 and 1-7 Release in Human Heart: Role of Cathepsin A","authors":"H. Jackman, M. Massad, M. Sekosan, F. Tan, V. Brovkovych, B. Marcic, E. G. Erdös","doi":"10.1161/01.HYP.0000017283.67962.02","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017283.67962.02","url":null,"abstract":"Human heart tissue enzymes cleave angiotensin (Ang) I to release Ang 1-9, Ang II, or Ang 1-7. In atrial homogenate preparations, cathepsin A (deamidase) is responsible for 65% of the liberated Ang 1-9. Ang 1-7 was released (88% to 100%) by a metallopeptidase, as established with peptidase inhibitors. Ang II was liberated to about equal degrees by ACE and chymase-type enzymes. Cathepsin A’s presence in heart tissue was also proven because it deamidated enkephalinamide substrate by immunoprecipitation of cathepsin A with antiserum to human recombinant enzyme and by immunohistochemistry. In immunohistochemistry, cathepsin A was detected in myocytes of atrial tissue. The products of Ang I cleavage, Ang 1-9 and Ang 1-7, potentiated the effect of an ACE-resistant bradykinin analog and enhanced kinin effect on the B2 receptor in Chinese hamster ovary cells transfected to express human ACE and B2 (CHO/AB), and in human pulmonary arterial endothelial cells. Ang 1-9 and 1-7 augmented arachidonic acid and nitric oxide (NO) release by kinin. Direct assay of NO liberation by bradykinin from endothelial cells was potentiated at 10 nmol/L concentration, 2.4-fold (Ang 1-9) and 2.1-fold (Ang 1-7); in higher concentrations, Ang 1-9 was significantly more active than Ang 1-7. Both peptides had traces of activity in the absence of bradykinin. Ang 1-9 and Ang 1-7 potentiated bradykinin action on the B2 receptor by raising arachidonic acid and NO release at much lower concentrations than their 50% inhibition concentrations (IC50s) with ACE. They probably induce conformational changes in the ACE/B2 receptor complex via interaction with ACE.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"107 1","pages":"976-981"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76246741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000016176.16042.2F
S. Taler, S. Textor, J. Augustine
Although resistant hypertension affects a minority of all hypertensives, this group continues to experience disproportionately high cardiovascular event rates despite newer antihypertensive agents. Hypertension represents an imbalance of hemodynamic forces within the circulation, usually characterized by elevated systemic vascular resistance. We studied the utility of serial hemodynamic parameters in the selection and titration of antihypertensive medication in resistant hypertensive patients using highly reproducible noninvasive measurements by thoracic bioimpedance. Resistant hypertension patients (n=104) were randomized to drug selection based either on serial hemodynamic (HD) measurements and a predefined algorithm or on drug selection directed by a hypertension specialist (SC) in a 3-month intensive treatment program. Blood pressure was lowered by intensified drug therapy in both treatment groups (169±3/87±2 to 139±2/72±1 mm Hg HD versus 173±3/91±2 to 147±2/79±1 mm Hg SC, P <0.01 for systolic and diastolic BP), using similar numbers and intensity of antihypertensive medications. Blood pressures were reduced further for those treated according to hemodynamic measurements, resulting in improved control rates (56% HD versus 33% SC controlled to ≤140/90 mm Hg, P <0.05) and incremental reduction in systemic vascular resistance measurements. Although the number of patients taking diuretics did not differ between groups, final diuretic dosage was higher in the hemodynamic cohort. Our results demonstrate superior blood pressure control using a treatment algorithm and serial hemodynamic measurements compared with clinical judgment alone in a randomized prospective study. Our measurements of thoracic fluid volume support occult volume expansion as a mediator of antihypertensive drug resistance and use of impedance measurements to guide advancing diuretic dose and adjustment of multidrug antihypertensive treatment.
尽管顽固性高血压只影响所有高血压患者中的一小部分，但尽管有较新的抗高血压药物，这一群体仍有不成比例的高心血管事件发生率。高血压是血液动力学力量在循环中的不平衡，通常以全身血管阻力升高为特征。我们研究了一系列血液动力学参数在顽固性高血压患者抗高血压药物选择和滴定中的应用，采用高重复性的无创胸廓生物阻抗测量。在为期3个月的强化治疗方案中，顽固性高血压患者(n=104)根据连续血流动力学(HD)测量和预定义算法随机选择药物，或根据高血压专家(SC)指导的药物选择。两个治疗组在使用相同数量和强度的降压药物治疗后，血压均通过强化药物治疗降低(169±3/87±2至139±2/72±1 mm Hg HD vs 173±3/91±2至147±2/79±1 mm Hg SC，收缩压和舒张压P <0.01)。根据血流动力学测量进行治疗的患者血压进一步降低，导致控制率提高(56% HD vs 33% SC控制在≤140/90 mm Hg, P <0.05)，全身血管阻力测量值逐渐降低。虽然服用利尿剂的患者数量在两组之间没有差异，但血液动力学组的最终利尿剂剂量更高。我们的研究结果表明，在一项随机前瞻性研究中，与单独的临床判断相比，使用治疗算法和一系列血流动力学测量的血压控制优于临床判断。我们测量胸腔液体容量支持隐性容量扩张作为抗高血压药物耐药的中介，并使用阻抗测量来指导推进利尿剂剂量和调整多药抗高血压治疗。
{"title":"Resistant Hypertension: Comparing Hemodynamic Management to Specialist Care","authors":"S. Taler, S. Textor, J. Augustine","doi":"10.1161/01.HYP.0000016176.16042.2F","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016176.16042.2F","url":null,"abstract":"Although resistant hypertension affects a minority of all hypertensives, this group continues to experience disproportionately high cardiovascular event rates despite newer antihypertensive agents. Hypertension represents an imbalance of hemodynamic forces within the circulation, usually characterized by elevated systemic vascular resistance. We studied the utility of serial hemodynamic parameters in the selection and titration of antihypertensive medication in resistant hypertensive patients using highly reproducible noninvasive measurements by thoracic bioimpedance. Resistant hypertension patients (n=104) were randomized to drug selection based either on serial hemodynamic (HD) measurements and a predefined algorithm or on drug selection directed by a hypertension specialist (SC) in a 3-month intensive treatment program. Blood pressure was lowered by intensified drug therapy in both treatment groups (169±3/87±2 to 139±2/72±1 mm Hg HD versus 173±3/91±2 to 147±2/79±1 mm Hg SC, P <0.01 for systolic and diastolic BP), using similar numbers and intensity of antihypertensive medications. Blood pressures were reduced further for those treated according to hemodynamic measurements, resulting in improved control rates (56% HD versus 33% SC controlled to ≤140/90 mm Hg, P <0.05) and incremental reduction in systemic vascular resistance measurements. Although the number of patients taking diuretics did not differ between groups, final diuretic dosage was higher in the hemodynamic cohort. Our results demonstrate superior blood pressure control using a treatment algorithm and serial hemodynamic measurements compared with clinical judgment alone in a randomized prospective study. Our measurements of thoracic fluid volume support occult volume expansion as a mediator of antihypertensive drug resistance and use of impedance measurements to guide advancing diuretic dose and adjustment of multidrug antihypertensive treatment.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"70 1","pages":"982-988"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86248553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000017827.63253.16
A. Pachori, M. Numan, C. Ferrario, D. Diz, M. Raizada, M. Katovich
Our studies have established that a single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense gene causes prolonged antihypertensive actions in the spontaneously hypertensive rat. These results suggest that antisense gene therapy is a conceptually valid strategy for the control of hypertension at the genetic level. To evaluate whether attenuation of the pathophysiological aspects of hypertension are dependent on the blood pressure lowering actions of antisense gene therapy, we chose the renin transgenic rat as a hypertensive animal model and cardiac hypertrophy as the hypertension-associated pathophysiology. A single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense in the neonatal rat resulted in long-term expression of the antisense transgene in various cardiovascular-relevant tissues, including the heart. This expression was associated with a significant attenuation of cardiac hypertrophy despite its failure to normalize high blood pressure. Developmental studies indicated that cardiac hypertrophy was evident as early as 16 days of age in viral vector–treated control transgenic rats, despite these animals exhibiting normal blood pressure. These observations demonstrate that, in the renin-transgenic rat, the onset of cardiac hypertrophy occurs during development and is prevented without normalization of high blood pressure. Collectively, these results provide further proof of the concept and indicate that antisense gene therapy could successfully target the local tissues’ renin-angiotensin system to produce beneficial cardiovascular outcomes.
{"title":"Blood Pressure–Independent Attenuation of Cardiac Hypertrophy by AT1R-AS Gene Therapy","authors":"A. Pachori, M. Numan, C. Ferrario, D. Diz, M. Raizada, M. Katovich","doi":"10.1161/01.HYP.0000017827.63253.16","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017827.63253.16","url":null,"abstract":"Our studies have established that a single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense gene causes prolonged antihypertensive actions in the spontaneously hypertensive rat. These results suggest that antisense gene therapy is a conceptually valid strategy for the control of hypertension at the genetic level. To evaluate whether attenuation of the pathophysiological aspects of hypertension are dependent on the blood pressure lowering actions of antisense gene therapy, we chose the renin transgenic rat as a hypertensive animal model and cardiac hypertrophy as the hypertension-associated pathophysiology. A single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense in the neonatal rat resulted in long-term expression of the antisense transgene in various cardiovascular-relevant tissues, including the heart. This expression was associated with a significant attenuation of cardiac hypertrophy despite its failure to normalize high blood pressure. Developmental studies indicated that cardiac hypertrophy was evident as early as 16 days of age in viral vector–treated control transgenic rats, despite these animals exhibiting normal blood pressure. These observations demonstrate that, in the renin-transgenic rat, the onset of cardiac hypertrophy occurs during development and is prevented without normalization of high blood pressure. Collectively, these results provide further proof of the concept and indicate that antisense gene therapy could successfully target the local tissues’ renin-angiotensin system to produce beneficial cardiovascular outcomes.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"19 1","pages":"969-975"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88113212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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