Pub Date : 2002-07-01DOI: 10.1161/01.HYP.0000022806.87281.62
A. W. Miller, C. Tulbert, M. Puskar, D. Busija
Although insulin-mediated vasodilation is impaired in insulin resistance, the mechanisms of this are unknown. We investigated factors mediating vasoactive responses to insulin in control and insulin-resistant rats. Responses to insulin in small mesenteric arteries from control and insulin-resistant rats were investigated after blocking endothelin-A receptors, cyclooxygenase, nitric oxide synthase, and potassium channels. In addition, insulin’s effect on prostacyclin production in small mesenteric blood vessels was assessed by enzyme immunoassay. Insulin induced a concentration-dependent vasodilation in control arteries that was absent in arteries from insulin-resistant rats. However, in the presence of BQ610, an endothelin-A receptor antagonist, the response to insulin was normalized in insulin-resistant arteries. In control arteries, insulin-induced vasodilation was completely inhibited by indomethacin, meclofenamate, glibenclamide, or potassium chloride. In contrast, neither n-nitro-l-arginine nor the combination of charybdotoxin and apamin altered vasodilation to insulin. In insulin-resistant arteries in the presence of BQ610, vasodilation was also inhibited by indomethacin, glibenclamide, and potassium chloride. Insulin increased prostacyclin production in small mesenteric blood vessels from both groups of rats to a similar degree. Insulin-induced vasodilation in small rat mesenteric arteries is mediated through prostacyclin- and ATP-dependent potassium channels. However, insulin-resistant arteries do not vasodilate to insulin unless endothelin-A receptors are blocked. Thus, impaired relaxation to insulin in insulin-resistant rats is due to enhanced vasoconstriction by endothelin, which offsets a normal vasodilatory response to insulin.
{"title":"Enhanced Endothelin Activity Prevents Vasodilation to Insulin in Insulin Resistance","authors":"A. W. Miller, C. Tulbert, M. Puskar, D. Busija","doi":"10.1161/01.HYP.0000022806.87281.62","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022806.87281.62","url":null,"abstract":"Although insulin-mediated vasodilation is impaired in insulin resistance, the mechanisms of this are unknown. We investigated factors mediating vasoactive responses to insulin in control and insulin-resistant rats. Responses to insulin in small mesenteric arteries from control and insulin-resistant rats were investigated after blocking endothelin-A receptors, cyclooxygenase, nitric oxide synthase, and potassium channels. In addition, insulin’s effect on prostacyclin production in small mesenteric blood vessels was assessed by enzyme immunoassay. Insulin induced a concentration-dependent vasodilation in control arteries that was absent in arteries from insulin-resistant rats. However, in the presence of BQ610, an endothelin-A receptor antagonist, the response to insulin was normalized in insulin-resistant arteries. In control arteries, insulin-induced vasodilation was completely inhibited by indomethacin, meclofenamate, glibenclamide, or potassium chloride. In contrast, neither n-nitro-l-arginine nor the combination of charybdotoxin and apamin altered vasodilation to insulin. In insulin-resistant arteries in the presence of BQ610, vasodilation was also inhibited by indomethacin, glibenclamide, and potassium chloride. Insulin increased prostacyclin production in small mesenteric blood vessels from both groups of rats to a similar degree. Insulin-induced vasodilation in small rat mesenteric arteries is mediated through prostacyclin- and ATP-dependent potassium channels. However, insulin-resistant arteries do not vasodilate to insulin unless endothelin-A receptors are blocked. Thus, impaired relaxation to insulin in insulin-resistant rats is due to enhanced vasoconstriction by endothelin, which offsets a normal vasodilatory response to insulin.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"16 1","pages":"78-82"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84735024","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 : 2002-07-01DOI: 10.1161/01.HYP.0000022693.11752.E9
J. Cui, J. Hopper, S. Harrap
The correlations between systolic blood pressure (SBP) and diastolic blood pressure (DBP), and between SBP and body mass index (BMI), might result from genetic or environmental factors that determine variation in 2 or more phenotypes and are shared by family members. In 767 adult nuclear families (n=2912 individuals, including 66 pairs of monozygotic twins and 84 pairs of dizygotic twins), we used a multivariate normal model and the software FISHER to estimate genetic and environmental components of variation and covariation. Mean phenotypes were adjusted for age, gender, and generation, and for antihypertensive treatment. Genetic and shared family environmental factors accounted for 46% and 31% of total variance in SBP, respectively. Adjustment of SBP for DBP reduced considerably both the additive genetic (86.7 to 21.0) and shared environmental (59.7 to 21.0) components of variance. Smaller reductions in genetic (86.7 to 84.9) and shared environmental (59.7 to 51.1) components were observed after adjustment of SBP for BMI. For SBP and DBP, the correlation between the effects of genes was 1.00 and between shared environmental effects was 0.52. For SBP and BMI the correlations were 0.30 for genetic and 0.22 for shared environmental effects. Our findings suggest that the same genes and many of the same family environmental factors determine variation in both SBP and DBP. In contrast, SBP and BMI share genetic and family environmental determinants to a lesser degree. These observations are relevant to multifactorial cardiovascular risk reduction based on genetic and family environmental approaches.
{"title":"Genes and Family Environment Explain Correlations Between Blood Pressure and Body Mass Index","authors":"J. Cui, J. Hopper, S. Harrap","doi":"10.1161/01.HYP.0000022693.11752.E9","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022693.11752.E9","url":null,"abstract":"The correlations between systolic blood pressure (SBP) and diastolic blood pressure (DBP), and between SBP and body mass index (BMI), might result from genetic or environmental factors that determine variation in 2 or more phenotypes and are shared by family members. In 767 adult nuclear families (n=2912 individuals, including 66 pairs of monozygotic twins and 84 pairs of dizygotic twins), we used a multivariate normal model and the software FISHER to estimate genetic and environmental components of variation and covariation. Mean phenotypes were adjusted for age, gender, and generation, and for antihypertensive treatment. Genetic and shared family environmental factors accounted for 46% and 31% of total variance in SBP, respectively. Adjustment of SBP for DBP reduced considerably both the additive genetic (86.7 to 21.0) and shared environmental (59.7 to 21.0) components of variance. Smaller reductions in genetic (86.7 to 84.9) and shared environmental (59.7 to 51.1) components were observed after adjustment of SBP for BMI. For SBP and DBP, the correlation between the effects of genes was 1.00 and between shared environmental effects was 0.52. For SBP and BMI the correlations were 0.30 for genetic and 0.22 for shared environmental effects. Our findings suggest that the same genes and many of the same family environmental factors determine variation in both SBP and DBP. In contrast, SBP and BMI share genetic and family environmental determinants to a lesser degree. These observations are relevant to multifactorial cardiovascular risk reduction based on genetic and family environmental approaches.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"6 1","pages":"7-12"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81691447","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 : 2002-07-01DOI: 10.1161/01.HYP.0000023226.50264.42
Yosuke Mori, T. Nishikimi, N. Kobayashi, H. Ono, K. Kangawa, H. Matsuoka
Previous studies have demonstrated that adrenomedullin has inhibitory effects on the proliferation and DNA synthesis of mesangial cells and vascular smooth muscle cells in vitro and that plasma adrenomedullin levels are markedly elevated in malignant hypertension. This study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in malignant hypertensive rats. We studied the following 3 groups: control Wistar Kyoto rats, deoxycorticosterone acetate–salt spontaneously hypertensive rats, and adrenomedullin-treated deoxycorticosterone acetate–salt spontaneously hypertensive rats. Chronic adrenomedullin infusion using an osmotic minipump was started simultaneously with deoxycorticosterone acetate–salt treatment. After 3 weeks of the treatment, malignant hypertensive rats were characterized by higher blood pressure, kidney weight, urinary protein excretion, glomerular injury score, plasma renin concentration, aldosterone level, endogenous rat plasma adrenomedullin level, renal cortical tissue angiotensin II level, angiotensin-converting enzyme mRNA level, and transforming growth factor-&bgr;1 mRNA level in the renal cortex, and by lower creatinine clearance, compared with the control rats. Chronic adrenomedullin infusion significantly improved these parameters (kidney weight −6.5%, urinary protein excretion −63.8%, glomerular injury score −38.3%, plasma renin concentration −52.4%, aldosterone −23.2%, rat adrenomedullin −28.6%, renal angiotensin II −28.1%, renal angiotensin-converting enzyme mRNA −38.3%, renal transforming growth factor-&bgr;1 mRNA −56.2%, and creatinine clearance +20.5%) without significant reduction of mean arterial pressure (−4%). Kaplan-Meier survival analysis showed that adrenomedullin infusion significantly prolonged survival time. These results suggest that subdepressor dose of chronic adrenomedullin infusion has renoprotective effects in this malignant hypertension model, at least in part, via inhibition of the circulating and intrarenal renin-angiotensin system.
{"title":"Long-Term Adrenomedullin Infusion Improves Survival in Malignant Hypertensive Rats","authors":"Yosuke Mori, T. Nishikimi, N. Kobayashi, H. Ono, K. Kangawa, H. Matsuoka","doi":"10.1161/01.HYP.0000023226.50264.42","DOIUrl":"https://doi.org/10.1161/01.HYP.0000023226.50264.42","url":null,"abstract":"Previous studies have demonstrated that adrenomedullin has inhibitory effects on the proliferation and DNA synthesis of mesangial cells and vascular smooth muscle cells in vitro and that plasma adrenomedullin levels are markedly elevated in malignant hypertension. This study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in malignant hypertensive rats. We studied the following 3 groups: control Wistar Kyoto rats, deoxycorticosterone acetate–salt spontaneously hypertensive rats, and adrenomedullin-treated deoxycorticosterone acetate–salt spontaneously hypertensive rats. Chronic adrenomedullin infusion using an osmotic minipump was started simultaneously with deoxycorticosterone acetate–salt treatment. After 3 weeks of the treatment, malignant hypertensive rats were characterized by higher blood pressure, kidney weight, urinary protein excretion, glomerular injury score, plasma renin concentration, aldosterone level, endogenous rat plasma adrenomedullin level, renal cortical tissue angiotensin II level, angiotensin-converting enzyme mRNA level, and transforming growth factor-&bgr;1 mRNA level in the renal cortex, and by lower creatinine clearance, compared with the control rats. Chronic adrenomedullin infusion significantly improved these parameters (kidney weight −6.5%, urinary protein excretion −63.8%, glomerular injury score −38.3%, plasma renin concentration −52.4%, aldosterone −23.2%, rat adrenomedullin −28.6%, renal angiotensin II −28.1%, renal angiotensin-converting enzyme mRNA −38.3%, renal transforming growth factor-&bgr;1 mRNA −56.2%, and creatinine clearance +20.5%) without significant reduction of mean arterial pressure (−4%). Kaplan-Meier survival analysis showed that adrenomedullin infusion significantly prolonged survival time. These results suggest that subdepressor dose of chronic adrenomedullin infusion has renoprotective effects in this malignant hypertension model, at least in part, via inhibition of the circulating and intrarenal renin-angiotensin system.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"61 4 1","pages":"107-113"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89800770","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 : 2002-07-01DOI: 10.1161/01.HYP.0000019972.37690.EF
M. Cruz, Terry T Huang, Maria S. Johnson, B. Gower, M. Goran
Although insulin sensitivity is correlated with high blood pressure in adults, it is unclear whether such a relationship exists in children across ethnic groups. Therefore, the aims of the study were to establish (1) if body composition and insulin sensitivity were related to blood pressure in children, and (2) if any differences in blood pressure between white and black children were explained by body composition and/or insulin sensitivity. Insulin sensitivity and the acute insulin response were established by the minimal model and body composition by dual-energy X-ray absorptiometry. Blood pressure was recorded in the supine position. Body composition, fasting insulin (P <0.01), and the acute insulin response (P <0.05) were positively related to systolic blood pressure but not to diastolic blood pressure, and insulin sensitivity (P <0.001) was negatively related to systolic blood pressure but not to diastolic blood pressure. Insulin sensitivity was negatively associated with systolic and diastolic blood pressure after adjustment for body composition (P <0.01). Black children had higher systolic (110±9.2 versus 105±8.5 mm Hg, P =0.01) and diastolic (59±7.0 versus 54±8.0 mm Hg, P <0.01) blood pressure than did white children. The ethnic difference in blood pressure was not explained by body composition, fasting insulin, acute insulin response, or insulin sensitivity. In conclusion, the relationship between insulin sensitivity and systolic blood pressure is evident early in life. Black ethnicity and low insulin sensitivity contribute independently to higher blood pressure in children.
尽管胰岛素敏感性与成人高血压相关,但尚不清楚这种关系是否存在于不同种族的儿童中。因此,本研究的目的是确定(1)身体成分和胰岛素敏感性是否与儿童血压有关,以及(2)白人和黑人儿童之间的血压差异是否可以用身体成分和/或胰岛素敏感性来解释。通过最小模型和双能x线吸收仪建立胰岛素敏感性和急性胰岛素反应。在仰卧位记录血压。体成分、空腹胰岛素(P <0.01)、急性胰岛素反应(P <0.05)与收缩压呈正相关,与舒张压无相关;胰岛素敏感性(P <0.001)与收缩压呈负相关,与舒张压无相关。调整体成分后,胰岛素敏感性与收缩压和舒张压呈负相关(P <0.01)。黑人儿童的收缩压(110±9.2比105±8.5 mm Hg, P =0.01)和舒张压(59±7.0比54±8.0 mm Hg, P <0.01)高于白人儿童。血压的种族差异不能用身体成分、空腹胰岛素、急性胰岛素反应或胰岛素敏感性来解释。总之,胰岛素敏感性和收缩压之间的关系在生命早期就很明显。黑人和低胰岛素敏感性是儿童高血压的独立诱因。
{"title":"Insulin Sensitivity and Blood Pressure in Black and White Children","authors":"M. Cruz, Terry T Huang, Maria S. Johnson, B. Gower, M. Goran","doi":"10.1161/01.HYP.0000019972.37690.EF","DOIUrl":"https://doi.org/10.1161/01.HYP.0000019972.37690.EF","url":null,"abstract":"Although insulin sensitivity is correlated with high blood pressure in adults, it is unclear whether such a relationship exists in children across ethnic groups. Therefore, the aims of the study were to establish (1) if body composition and insulin sensitivity were related to blood pressure in children, and (2) if any differences in blood pressure between white and black children were explained by body composition and/or insulin sensitivity. Insulin sensitivity and the acute insulin response were established by the minimal model and body composition by dual-energy X-ray absorptiometry. Blood pressure was recorded in the supine position. Body composition, fasting insulin (P <0.01), and the acute insulin response (P <0.05) were positively related to systolic blood pressure but not to diastolic blood pressure, and insulin sensitivity (P <0.001) was negatively related to systolic blood pressure but not to diastolic blood pressure. Insulin sensitivity was negatively associated with systolic and diastolic blood pressure after adjustment for body composition (P <0.01). Black children had higher systolic (110±9.2 versus 105±8.5 mm Hg, P =0.01) and diastolic (59±7.0 versus 54±8.0 mm Hg, P <0.01) blood pressure than did white children. The ethnic difference in blood pressure was not explained by body composition, fasting insulin, acute insulin response, or insulin sensitivity. In conclusion, the relationship between insulin sensitivity and systolic blood pressure is evident early in life. Black ethnicity and low insulin sensitivity contribute independently to higher blood pressure in children.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"118 ","pages":"18-22"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91552859","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 : 2002-07-01DOI: 10.1161/01.HYP.0000023182.68420.EB
G. Rossi, V. Di Bello, C. Ganzaroli, A. Sacchetto, M. Cesari, A. Bertini, D. Giorgi, R. Scognamiglio, M. Mariani, A. Pessina
Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P ≤0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7±1.8 versus 45.5±2.0 g/m2.7;P =0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVIs; −12.02±5.84% versus 6.06±3.08%;P =0.012) and posterior wall (−11.13±6.42% versus 8.63±9.62%;P =0.012). A regression analysis showed that CVIs was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for ≈36% of CVIs variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval.
实验表明,高醛固酮增多症与心肌间质纤维化有因果关系,但尚不清楚这种联系是否也适用于人类。因此,我们研究了原发性醛固酮增多症(PA)引起的过量醛固酮对心脏胶原沉积的影响。我们使用超声心动图估计左心室(LV)壁厚度和尺寸,并对17例连续的PA患者和10例原发性(原发性)高血压患者的心肌质地进行视频密度分析,这些患者在人口统计学、随意血压和已知高血压持续时间方面相匹配。两组在血清K+、心电图PQ间隔时间、血浆肾素活性和醛固酮水平方面存在差异(P均≤0.002),但在随意血压值、人口统计学和高血压持续时间方面没有差异。与高血压患者相比,PA患者的左室质量指数(53.7±1.8)高于高血压患者(45.5±2.0 g/m2.7, P =0.008),心肌间隔平均灰度循环变异指数(CVIs;- 12.02±5.84%比6.06±3.08%,P =0.012)和后壁(- 11.13±6.42%比8.63±9.62%,P =0.012)。回归分析显示,PQ持续时间、仰卧位血浆肾素活性、血浆醛固酮和年龄可以预测CVIs,这些因素合计占CVIs方差的约36%。PA与心肌结构改变有关,表明胶原沉积增加,这可以解释左室舒张充盈依赖于收缩前和PQ间期延长。
{"title":"Excess ldosterone Is Associated With Alterations of Myocardial Texture in Primary Aldosteronism","authors":"G. Rossi, V. Di Bello, C. Ganzaroli, A. Sacchetto, M. Cesari, A. Bertini, D. Giorgi, R. Scognamiglio, M. Mariani, A. Pessina","doi":"10.1161/01.HYP.0000023182.68420.EB","DOIUrl":"https://doi.org/10.1161/01.HYP.0000023182.68420.EB","url":null,"abstract":"Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P ≤0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7±1.8 versus 45.5±2.0 g/m2.7;P =0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVIs; −12.02±5.84% versus 6.06±3.08%;P =0.012) and posterior wall (−11.13±6.42% versus 8.63±9.62%;P =0.012). A regression analysis showed that CVIs was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for ≈36% of CVIs variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"8 1","pages":"23-27"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87937055","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 : 2002-07-01DOI: 10.1161/01.HYP.0000022061.12297.2E
C. C. Spencer, D. Gurney, A. Blann, D. Beevers, G. Y. Lip
To investigate the relationship between soluble markers of platelet, endothelial and rheological function, and target organ damage and their response to intensified management in a population of middle-age hypertensive patients at high risk of cardiovascular complications, we studied 382 consecutive patients (308 men; mean age, 63 years, SD 8) along with 60 normotensive controls free of cardiovascular disease. Patients were divided into those with target organ damage (TOD; n=107) and those free of end-organ damage. Plasma levels of soluble P-selectin (sP-sel), a marker of platelet activation, and von Willebrand factor (vWF), an index of endothelial damage/dysfunction (both enzyme-linked immunosorbent assay), and the rheological indices fibrinogen, plasma viscosity, hematocrit, platelet, and white cell count were measured. In 53 patients, variables were further measured after 6 months of intensified cardiovascular risk management. Patients with TOD had significantly higher vWF, 137 (SD 33) versus 125 (SD 33) IU/dL (P =0.002,) and a greater proportion of smokers, 31% versus 16% (P =0.002). There were no statistically significant differences in plasma viscosity, fibrinogen, hematocrit, white blood cell count, platelet count, or sP-sel between the 2 subgroups. In multivariate analysis, vWF was a significant independent predictor for TOD. After 6 months of intensified management in 53 patients who entered the trial, there were significant reductions in systolic blood pressure, total cholesterol, hematocrit, plasma viscosity, sP-sel, and vWF (all P <0.01) but no significant change in fibrinogen. In conclusion, there is a relationship between TOD and endothelial damage/dysfunction in hypertension. Intensified management results in improvements in hemorheology, endothelial and platelet function.
{"title":"Von Willebrand Factor, Soluble P-Selectin, and Target Organ Damage in Hypertension: A Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)","authors":"C. C. Spencer, D. Gurney, A. Blann, D. Beevers, G. Y. Lip","doi":"10.1161/01.HYP.0000022061.12297.2E","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022061.12297.2E","url":null,"abstract":"To investigate the relationship between soluble markers of platelet, endothelial and rheological function, and target organ damage and their response to intensified management in a population of middle-age hypertensive patients at high risk of cardiovascular complications, we studied 382 consecutive patients (308 men; mean age, 63 years, SD 8) along with 60 normotensive controls free of cardiovascular disease. Patients were divided into those with target organ damage (TOD; n=107) and those free of end-organ damage. Plasma levels of soluble P-selectin (sP-sel), a marker of platelet activation, and von Willebrand factor (vWF), an index of endothelial damage/dysfunction (both enzyme-linked immunosorbent assay), and the rheological indices fibrinogen, plasma viscosity, hematocrit, platelet, and white cell count were measured. In 53 patients, variables were further measured after 6 months of intensified cardiovascular risk management. Patients with TOD had significantly higher vWF, 137 (SD 33) versus 125 (SD 33) IU/dL (P =0.002,) and a greater proportion of smokers, 31% versus 16% (P =0.002). There were no statistically significant differences in plasma viscosity, fibrinogen, hematocrit, white blood cell count, platelet count, or sP-sel between the 2 subgroups. In multivariate analysis, vWF was a significant independent predictor for TOD. After 6 months of intensified management in 53 patients who entered the trial, there were significant reductions in systolic blood pressure, total cholesterol, hematocrit, plasma viscosity, sP-sel, and vWF (all P <0.01) but no significant change in fibrinogen. In conclusion, there is a relationship between TOD and endothelial damage/dysfunction in hypertension. Intensified management results in improvements in hemorheology, endothelial and platelet function.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"128 1","pages":"61-66"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74800963","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 : 2002-06-01DOI: 10.1161/01.HYP.0000018825.76673.EA
N. Benowitz, Anna Hansson, P. Jacob
The purpose of this study was to compare circadian blood pressure and heart rate patterns and other cardiovascular effects of nicotine delivered rapidly (via nasal spray, NNS), slowly (transdermal nicotine, TDN), by cigarette smoking (rapid delivery of nicotine plus other smoke toxins), and placebo NNS. Twelve healthy cigarette smokers were studied on a research ward when they smoked cigarettes (16 per day) or used TDN (15 mg/16 h), NNS (24 1-mg doses per day), or placebo NNS, each for 5 days. There were no significant differences in systolic blood pressure, but diastolic blood pressure was slightly increased during cigarette smoking. Plasma epinephrine, &bgr;-thromboglobulin, and fibrinogen levels were higher during cigarette smoking than with TDN. For most measurements, NNS values were intermediate between and not significantly different from those of cigarette smoking and TDN. We conclude that, at recommended doses, TDN and NNS have fewer effects on biomarkers of cardiovascular risk than does cigarette smoking.
{"title":"Cardiovascular Effects of Nasal and Transdermal Nicotine and Cigarette Smoking","authors":"N. Benowitz, Anna Hansson, P. Jacob","doi":"10.1161/01.HYP.0000018825.76673.EA","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018825.76673.EA","url":null,"abstract":"The purpose of this study was to compare circadian blood pressure and heart rate patterns and other cardiovascular effects of nicotine delivered rapidly (via nasal spray, NNS), slowly (transdermal nicotine, TDN), by cigarette smoking (rapid delivery of nicotine plus other smoke toxins), and placebo NNS. Twelve healthy cigarette smokers were studied on a research ward when they smoked cigarettes (16 per day) or used TDN (15 mg/16 h), NNS (24 1-mg doses per day), or placebo NNS, each for 5 days. There were no significant differences in systolic blood pressure, but diastolic blood pressure was slightly increased during cigarette smoking. Plasma epinephrine, &bgr;-thromboglobulin, and fibrinogen levels were higher during cigarette smoking than with TDN. For most measurements, NNS values were intermediate between and not significantly different from those of cigarette smoking and TDN. We conclude that, at recommended doses, TDN and NNS have fewer effects on biomarkers of cardiovascular risk than does cigarette smoking.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"39 1","pages":"1107-1112"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81972416","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 : 2002-06-01DOI: 10.1161/01.HYP.0000018590.26853.C7
S. Ye, Huiquin Zhong, V. Duong, V. Campese
We have developed a new model of neurogenic hypertension in the rat, in which hypertension is caused by injecting 50 &mgr;L of 10% phenol in the lower pole of one kidney. Administration of phenol in the kidney causes an immediate and persistent rise in blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity (RSNA). Because angiotensin II (Ang II) is known to stimulate central and peripheral sympathetic nervous system (SNS) activity, we have tested the hypothesis that losartan, a specific Ang II AT1 receptor antagonist, may lower BP, at least in part, by SNS inhibition. To this end, we studied the effects of losartan on BP and SNS activity following intrarenal phenol injection. Central SNS activity was measured by NE secretion from the PH using a microdialysis technique, and peripheral SNS activity was measured by direct recording of renal nerve activity. At the end of the experiments, brains were isolated and interleukin (IL)-1&bgr; and nitric oxide synthase (NOS) mRNA gene expression was measured by RT-PCR in the PH, paraventricular nuclei (PVN), and locus ceruleus (LC). The intrarenal injection of phenol raised BP, as well as central and renal SNS activity, but reduced the abundance of IL-1&bgr; and neuronal NOS (nNOS) mRNA in the PH, PVN, and LC. Whether injected intravenously or in the lateral ventricle, losartan caused a significant (P <0.01) and dose-dependent inhibition of the effects of phenol on BP, NE secretion from the PH, and RSNA. Losartan also caused a significant (P <0.01) and dose-dependent rise in IL-1&bgr; and nNOS-mRNA gene expression in the PH, PVN, and LC of phenol-injected rats. In conclusion, these studies have shown that the intrarenal injection of phenol causes a rise in central and renal SNS activity and a decrease in IL-1&bgr; and nNOS-mRNA in the PH, PVN, and LC. Losartan prevented the rise in BP and SNS activity, as well as the decrease in IL-1&bgr; and nNOS mRNA abundance caused by phenol. These studies have demonstrated that the antihypertensive action of losartan in the phenol renal injury model is largely mediated by inhibition of central and peripheral SNS activity and suggest that activation of IL-1&bgr; and nNOS, 2 important modulators of central SNS activity, mediates the inhibitory action of losartan on SNS activity.
我们建立了一种新的大鼠神经源性高血压模型,在一个肾的下极注射50 μ L 10%的苯酚引起高血压。在肾脏中使用苯酚会引起血压(BP)、下丘脑后核(PH)分泌去甲肾上腺素(NE)和肾交感神经活动(RSNA)的立即和持续升高。由于已知血管紧张素II (Ang II)能刺激中枢和周围交感神经系统(SNS)的活性,我们已经验证了氯沙坦(一种特异性的Ang II AT1受体拮抗剂)可能通过抑制SNS降低血压的假设。为此,我们研究了氯沙坦对静脉注射苯酚后血压和SNS活性的影响。中枢SNS活动通过微透析技术从PH分泌NE来测量,外周SNS活动通过直接记录肾神经活动来测量。在实验结束时,分离脑,白细胞介素(IL)-1&bgr;采用RT-PCR法检测PH、室旁核(PVN)和蓝核座(LC)中一氧化氮合酶(NOS) mRNA基因的表达。肾内注射苯酚使血压升高,中央和肾脏SNS活性升高,但IL-1&bgr丰度降低;PH、PVN和LC中神经元NOS mRNA的表达。无论是静脉注射还是侧脑室注射,氯沙坦对苯酚对BP、PH分泌NE和RSNA的影响均有显著(P <0.01)且剂量依赖性的抑制作用。氯沙坦也引起IL-1&bgr显著升高(P <0.01),且呈剂量依赖性;苯酚注射大鼠PH、PVN和LC中nNOS-mRNA基因表达的变化。总之,这些研究表明,肾内注射苯酚导致中央和肾脏SNS活性升高,il -1和bgr降低;PH、PVN和LC中nNOS-mRNA的表达。氯沙坦抑制了BP和SNS活性的升高,抑制了il -1和bgr的降低;苯酚引起的nNOS mRNA丰度。这些研究表明氯沙坦在酚性肾损伤模型中的降压作用主要是通过抑制中枢和外周SNS活性介导的,并提示il -1的激活;2种重要的中枢SNS活性调节剂nNOS介导氯沙坦对SNS活性的抑制作用。
{"title":"Losartan Reduces Central and Peripheral Sympathetic Nerve Activity in a Rat Model of Neurogenic Hypertension","authors":"S. Ye, Huiquin Zhong, V. Duong, V. Campese","doi":"10.1161/01.HYP.0000018590.26853.C7","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018590.26853.C7","url":null,"abstract":"We have developed a new model of neurogenic hypertension in the rat, in which hypertension is caused by injecting 50 &mgr;L of 10% phenol in the lower pole of one kidney. Administration of phenol in the kidney causes an immediate and persistent rise in blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity (RSNA). Because angiotensin II (Ang II) is known to stimulate central and peripheral sympathetic nervous system (SNS) activity, we have tested the hypothesis that losartan, a specific Ang II AT1 receptor antagonist, may lower BP, at least in part, by SNS inhibition. To this end, we studied the effects of losartan on BP and SNS activity following intrarenal phenol injection. Central SNS activity was measured by NE secretion from the PH using a microdialysis technique, and peripheral SNS activity was measured by direct recording of renal nerve activity. At the end of the experiments, brains were isolated and interleukin (IL)-1&bgr; and nitric oxide synthase (NOS) mRNA gene expression was measured by RT-PCR in the PH, paraventricular nuclei (PVN), and locus ceruleus (LC). The intrarenal injection of phenol raised BP, as well as central and renal SNS activity, but reduced the abundance of IL-1&bgr; and neuronal NOS (nNOS) mRNA in the PH, PVN, and LC. Whether injected intravenously or in the lateral ventricle, losartan caused a significant (P <0.01) and dose-dependent inhibition of the effects of phenol on BP, NE secretion from the PH, and RSNA. Losartan also caused a significant (P <0.01) and dose-dependent rise in IL-1&bgr; and nNOS-mRNA gene expression in the PH, PVN, and LC of phenol-injected rats. In conclusion, these studies have shown that the intrarenal injection of phenol causes a rise in central and renal SNS activity and a decrease in IL-1&bgr; and nNOS-mRNA in the PH, PVN, and LC. Losartan prevented the rise in BP and SNS activity, as well as the decrease in IL-1&bgr; and nNOS mRNA abundance caused by phenol. These studies have demonstrated that the antihypertensive action of losartan in the phenol renal injury model is largely mediated by inhibition of central and peripheral SNS activity and suggest that activation of IL-1&bgr; and nNOS, 2 important modulators of central SNS activity, mediates the inhibitory action of losartan on SNS activity.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"16 1 1","pages":"1101-1106"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90145853","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 : 2002-06-01DOI: 10.1161/01.HYP.0000018588.56950.7A
Bing Li, A. Ogasawara, Renhui Yang, Wei Wei, G. He, T. F. Zioncheck, S. Bunting, A. D. de Vos, Hongkui Jin
Vascular endothelial growth factor (VEGF) exerts vasodilation-induced hypotension as a major side effect for treatment of ischemic diseases. VEGF has 2 receptor tyrosine kinases, KDR and Flt-1. Little is known about which receptor mediates VEGF-induced hypotension. To elucidate the role of each receptor in mediating hypotension, KDR-selective and Flt-1–selective mutants were used for in vitro and in vivo studies. The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF, whereas the Flt-1– selective mutant had no effect on proliferation. Intravenous injection of KDR-selective mutant, Flt-selective mutant, or VEGF caused a dose-related decrease in mean arterial pressure in conscious rats. The hypotensive response to KDR-selective mutant was significantly less than that to VEGF (P <0.01) but was greater than that to Flt-selective mutant (P <0.01). Similarly, VEGF and KDR-selective mutant induced more potent vasorelaxation than Flt-selective mutant or placenta growth factor that binds Flt-1 only (P <0.01), and the vasorelaxation to KDR-selective mutant was not significantly different at low concentrations but less than that to VEGF at high concentrations. The results indicate that the vasodilation and hypotensive effect of VEGF may involve both receptors, but KDR is the predominant receptor mediating this effect. Because KDR-selective mutant induced proliferation and angiogenesis similar to VEGF but was associated with 36% attenuation in hypotension, the data suggest that the KDR-selective mutant may represent an alternative treatment for ischemic diseases.
{"title":"KDR (VEGF Receptor 2) Is the Major Mediator for the Hypotensive Effect of VEGF","authors":"Bing Li, A. Ogasawara, Renhui Yang, Wei Wei, G. He, T. F. Zioncheck, S. Bunting, A. D. de Vos, Hongkui Jin","doi":"10.1161/01.HYP.0000018588.56950.7A","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018588.56950.7A","url":null,"abstract":"Vascular endothelial growth factor (VEGF) exerts vasodilation-induced hypotension as a major side effect for treatment of ischemic diseases. VEGF has 2 receptor tyrosine kinases, KDR and Flt-1. Little is known about which receptor mediates VEGF-induced hypotension. To elucidate the role of each receptor in mediating hypotension, KDR-selective and Flt-1–selective mutants were used for in vitro and in vivo studies. The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF, whereas the Flt-1– selective mutant had no effect on proliferation. Intravenous injection of KDR-selective mutant, Flt-selective mutant, or VEGF caused a dose-related decrease in mean arterial pressure in conscious rats. The hypotensive response to KDR-selective mutant was significantly less than that to VEGF (P <0.01) but was greater than that to Flt-selective mutant (P <0.01). Similarly, VEGF and KDR-selective mutant induced more potent vasorelaxation than Flt-selective mutant or placenta growth factor that binds Flt-1 only (P <0.01), and the vasorelaxation to KDR-selective mutant was not significantly different at low concentrations but less than that to VEGF at high concentrations. The results indicate that the vasodilation and hypotensive effect of VEGF may involve both receptors, but KDR is the predominant receptor mediating this effect. Because KDR-selective mutant induced proliferation and angiogenesis similar to VEGF but was associated with 36% attenuation in hypotension, the data suggest that the KDR-selective mutant may represent an alternative treatment for ischemic diseases.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"8 1","pages":"1095-1100"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89033762","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 : 2002-06-01DOI: 10.1161/01.HYP.0000019132.41066.95
P. Lantelme, C. Mestre, M. Lièvre, A. Gressard, H. Milon
Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) is an index of arterial stiffness, and its prognostic value has been repeatedly emphasized. The purpose of the present study was to assess the effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8±8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV was measured at 5 different pacing frequencies in the same session (60, 70, 80, 90, 100 bpm), the order of the various frequencies being randomly determined. Furthermore, to test the reproducibility, a repeat measurement of PWV was obtained in one randomly selected frequency. Blood pressure (BP) was measured by conventional means at each pacing frequency. PWV appeared fairly reproducible because no significant difference was disclosed between the 2 measurements obtained at the same HR level (P =0.5) and both measurements were strongly correlated (r =0.87, P <0.001). No significant BP variation was observed during pacing. There was a highly significant effect of HR on PWV estimated by a one-way, within-subjects analysis of variance (P =0.01). This study demonstrates that HR is an important factor in the intraindividual variation of PWV in elderly subjects. This raises methodological concern about the measurement of this parameter. Standardizing PWV for HR level seems mandatory if one wants to interpret PWV changes in clinical trials or in the follow-up of patients.
动脉僵硬度是心血管风险的重要决定因素。脉搏波速度(PWV)是动脉硬度的一项指标,其预后价值已被反复强调。本研究的目的是评估心率(HR)对PWV的影响。研究对象22例,平均年龄77.8±8.4 (SD)岁,永久性心脏起搏。每个受试者在同一时段内以5个不同的起搏频率(60,70,80,90,100bpm)测量PWV,各频率的顺序随机确定。此外,为了测试再现性,在一个随机选择的频率上获得了PWV的重复测量。采用常规方法测量各起搏频率的血压(BP)。PWV具有相当的可重复性,因为在相同HR水平下获得的两个测量值之间没有显着差异(P =0.5),并且两个测量值都具有强相关性(r =0.87, P <0.001)。起搏期间未观察到明显的血压变化。通过单因素、受试者内方差分析估计,HR对PWV的影响非常显著(P =0.01)。本研究表明,HR是导致老年人PWV个体差异的重要因素。这引起了对该参数测量方法的关注。如果想要在临床试验或患者随访中解释PWV的变化,标准化PWV的HR水平似乎是强制性的。
{"title":"Heart Rate: An Important Confounder of Pulse Wave Velocity Assessment","authors":"P. Lantelme, C. Mestre, M. Lièvre, A. Gressard, H. Milon","doi":"10.1161/01.HYP.0000019132.41066.95","DOIUrl":"https://doi.org/10.1161/01.HYP.0000019132.41066.95","url":null,"abstract":"Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) is an index of arterial stiffness, and its prognostic value has been repeatedly emphasized. The purpose of the present study was to assess the effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8±8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV was measured at 5 different pacing frequencies in the same session (60, 70, 80, 90, 100 bpm), the order of the various frequencies being randomly determined. Furthermore, to test the reproducibility, a repeat measurement of PWV was obtained in one randomly selected frequency. Blood pressure (BP) was measured by conventional means at each pacing frequency. PWV appeared fairly reproducible because no significant difference was disclosed between the 2 measurements obtained at the same HR level (P =0.5) and both measurements were strongly correlated (r =0.87, P <0.001). No significant BP variation was observed during pacing. There was a highly significant effect of HR on PWV estimated by a one-way, within-subjects analysis of variance (P =0.01). This study demonstrates that HR is an important factor in the intraindividual variation of PWV in elderly subjects. This raises methodological concern about the measurement of this parameter. Standardizing PWV for HR level seems mandatory if one wants to interpret PWV changes in clinical trials or in the follow-up of patients.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"51 1","pages":"1083-1087"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86158771","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}