Pub Date : 2003-01-01DOI: 10.1097/00005768-200305001-02223
M. Miyachi, A. Donato, Kenta Yamamoto, Kouki Takahashi, P. Gates, K. Moreau, Hirofumi Tanaka
Abstract—Reductions in the compliance of central arteries exert a number of adverse effects on systemic cardiovascular function and disease risk. Using the cross-sectional study design, we determined the relation between chronic resistance training and carotid arterial compliance. A total of 62 healthy normotensive men, 20 to 39 years of age (young) and 40 to 60 years of age (middle-aged), who were either sedentary or resistance-trained, were studied. In both activity groups, carotid arterial compliance (simultaneous ultrasound and applanation tonometry) was lower (P <0.05) in the middle-aged compared with the young men. There was no significant difference between young sedentary and resistance-trained men. In the middle-aged group, carotid arterial compliance in the resistance-trained men was ≈30% lower (P <0.01) than their sedentary peers. Femoral artery compliance and arm pulse wave velocity (measures of peripheral artery stiffness) were not different among any groups. Left ventricular hypertrophy index (echocardiography) was greater (P <0.05) in resistance-trained compared with sedentary men and was associated with carotid arterial compliance (r =−0.35;P <0.01). We concluded that (1) resistance training is associated with the smaller central arterial compliance in healthy middle-aged men; (2) age-related reductions in arterial compliance was greater in resistance-trained men than in sedentary men; and (3) the lower arterial compliance in the resistance-trained men is associated with left ventricular hypertrophy. In marked contrast to the beneficial effect of regular aerobic exercise, the present findings are not consistent with the idea that resistance training exerts beneficial influences on arterial wall buffering functions.
{"title":"Greater Age-Related Reductions in Central Arterial Compliance in Resistance-Trained Men","authors":"M. Miyachi, A. Donato, Kenta Yamamoto, Kouki Takahashi, P. Gates, K. Moreau, Hirofumi Tanaka","doi":"10.1097/00005768-200305001-02223","DOIUrl":"https://doi.org/10.1097/00005768-200305001-02223","url":null,"abstract":"Abstract—Reductions in the compliance of central arteries exert a number of adverse effects on systemic cardiovascular function and disease risk. Using the cross-sectional study design, we determined the relation between chronic resistance training and carotid arterial compliance. A total of 62 healthy normotensive men, 20 to 39 years of age (young) and 40 to 60 years of age (middle-aged), who were either sedentary or resistance-trained, were studied. In both activity groups, carotid arterial compliance (simultaneous ultrasound and applanation tonometry) was lower (P <0.05) in the middle-aged compared with the young men. There was no significant difference between young sedentary and resistance-trained men. In the middle-aged group, carotid arterial compliance in the resistance-trained men was ≈30% lower (P <0.01) than their sedentary peers. Femoral artery compliance and arm pulse wave velocity (measures of peripheral artery stiffness) were not different among any groups. Left ventricular hypertrophy index (echocardiography) was greater (P <0.05) in resistance-trained compared with sedentary men and was associated with carotid arterial compliance (r =−0.35;P <0.01). We concluded that (1) resistance training is associated with the smaller central arterial compliance in healthy middle-aged men; (2) age-related reductions in arterial compliance was greater in resistance-trained men than in sedentary men; and (3) the lower arterial compliance in the resistance-trained men is associated with left ventricular hypertrophy. In marked contrast to the beneficial effect of regular aerobic exercise, the present findings are not consistent with the idea that resistance training exerts beneficial influences on arterial wall buffering functions.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"525 ","pages":"130-135"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91459599","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 : 2002-12-01DOI: 10.1016/S0895-7061(03)00766-0
P. Mulatero, F. Rabbia, A. Milan, C. Paglieri, F. Morello, L. Chiandussi, F. Veglio
{"title":"Drug Effects on Aldosterone/Plasma Renin Activity Ratio in Primary Aldosteronism","authors":"P. Mulatero, F. Rabbia, A. Milan, C. Paglieri, F. Morello, L. Chiandussi, F. Veglio","doi":"10.1016/S0895-7061(03)00766-0","DOIUrl":"https://doi.org/10.1016/S0895-7061(03)00766-0","url":null,"abstract":"","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"48 1","pages":"897-902"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84795203","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 : 2002-08-01DOI: 10.1161/01.HYP.0000025904.23047.27
A. Mihailidou, M. Mardini, J. Funder, Matthew J. Raison
Elevated aldosterone levels induce a spironolactone-inhibitable decrease in cardiac sarcolemmal Na+-K+ pump function. Because pump inhibition has been shown to contribute to myocyte hypertrophy, restoration of Na+-K+ pump function may represent a possible mechanism for the cardioprotective action of mineralocorticoid receptor (MR) blockade. The present study examines whether treatment with the angiotensin type 1 receptor antagonist losartan, with either spironolactone or eplerenone, has additive effects on sarcolemmal Na+-K+ pump activity in hyperaldosteronemia. New Zealand White rabbits were divided into 7 different groups: controls, aldosterone alone, aldosterone plus spironolactone, aldosterone plus eplerenone, aldosterone plus losartan, aldosterone plus losartan and spironolactone, and aldosterone plus losartan and eplerenone. After 7 days, myocytes were isolated by enzymatic digestion. Electrogenic Na+-K+ pump current (Ip), arising from the 3:2 Na+:K+ exchange ratio, was measured by the whole-cell patch clamp technique. Elevated aldosterone levels lowered Ip; treatment with losartan reversed aldosterone-induced reduced pump function, as did MR blockade. Coadministration of spironolactone or eplerenone with losartan enhanced the losartan effect on pump function to a level similar to that measured in rabbits given losartan alone in the absence of hyperaldosteronemia. In conclusion, hyperaldosteronemia induces a decrease in Ip at near physiological levels of intracellular Na+ concentration. Treatment with losartan reverses this aldosterone-induced decrease in pump function, and coadministration with MR antagonists produces an additive effect on pump function, consistent with a beneficial effect of MR blockade in patients with hypertension and congestive heart failure treated with angiotensin type 1 receptor antagonists.
{"title":"Mineralocorticoid and Angiotensin Receptor Antagonism During Hyperaldosteronemia","authors":"A. Mihailidou, M. Mardini, J. Funder, Matthew J. Raison","doi":"10.1161/01.HYP.0000025904.23047.27","DOIUrl":"https://doi.org/10.1161/01.HYP.0000025904.23047.27","url":null,"abstract":"Elevated aldosterone levels induce a spironolactone-inhibitable decrease in cardiac sarcolemmal Na+-K+ pump function. Because pump inhibition has been shown to contribute to myocyte hypertrophy, restoration of Na+-K+ pump function may represent a possible mechanism for the cardioprotective action of mineralocorticoid receptor (MR) blockade. The present study examines whether treatment with the angiotensin type 1 receptor antagonist losartan, with either spironolactone or eplerenone, has additive effects on sarcolemmal Na+-K+ pump activity in hyperaldosteronemia. New Zealand White rabbits were divided into 7 different groups: controls, aldosterone alone, aldosterone plus spironolactone, aldosterone plus eplerenone, aldosterone plus losartan, aldosterone plus losartan and spironolactone, and aldosterone plus losartan and eplerenone. After 7 days, myocytes were isolated by enzymatic digestion. Electrogenic Na+-K+ pump current (Ip), arising from the 3:2 Na+:K+ exchange ratio, was measured by the whole-cell patch clamp technique. Elevated aldosterone levels lowered Ip; treatment with losartan reversed aldosterone-induced reduced pump function, as did MR blockade. Coadministration of spironolactone or eplerenone with losartan enhanced the losartan effect on pump function to a level similar to that measured in rabbits given losartan alone in the absence of hyperaldosteronemia. In conclusion, hyperaldosteronemia induces a decrease in Ip at near physiological levels of intracellular Na+ concentration. Treatment with losartan reverses this aldosterone-induced decrease in pump function, and coadministration with MR antagonists produces an additive effect on pump function, consistent with a beneficial effect of MR blockade in patients with hypertension and congestive heart failure treated with angiotensin type 1 receptor antagonists.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"8 1","pages":"124-129"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79179886","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 : 2002-08-01DOI: 10.1161/01.HYP.0000025880.56816.FA
S. Pokharel, S. Rasoul, A. Roks, R. V. van Leeuwen, M. V. van Luyn, L. Deelman, J. Smits, O. Carretero, W. V. van Gilst, Y. Pinto
N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a specific substrate for the N-terminal site of ACE and increases 5-fold during ACE inhibitor therapy. It is known to inhibit the proliferation of hematopoietic stem cells and has also recently been reported to inhibit the growth of cardiac fibroblasts. We investigated its mode of action in cardiac fibroblasts by assessing its influence on transforming growth factor &bgr;1 (TGF&bgr;1)–mediated Smad signaling. AcSDKP inhibited the proliferation of isolated cardiac fibroblasts (P <0.05) but significantly stimulated the proliferation of vascular smooth muscle cells. Flow cytometry of rat cardiac fibroblasts treated with AcSDKP showed significant inhibition of the progression of cells from G0/G1 phase to S phase of the cell cycle. In cardiac fibroblasts transfected with a Smad-sensitive luciferase reporter construct, AcSDKP decreased luciferase activity by 55±9.7% (P =0.01). Moreover, phosphorylation and nuclear translocation of Smad2 was decreased in cardiac fibroblasts treated with AcSDKP. To conclude, AcSDKP inhibits the growth of cardiac fibroblasts and also inhibits TGF&bgr;1-stimulated phosphorylation of Smad2. Because AcSDKP increases substantially during ACE inhibitor therapy, this suggests a novel pathway independent of angiotensin II, by which ACE inhibitors can inhibit cardiac fibrosis.
n -乙酰基ser - asp - lys - pro (AcSDKP)是ACE n末端的特异性底物，在ACE抑制剂治疗期间增加5倍。已知它能抑制造血干细胞的增殖，最近也有报道称它能抑制心脏成纤维细胞的生长。我们通过评估其对转化生长因子&bgr;1 (TGF&bgr;1)介导的Smad信号传导的影响来研究其在心脏成纤维细胞中的作用模式。AcSDKP抑制离体心肌成纤维细胞的增殖(P <0.05)，但显著刺激血管平滑肌细胞的增殖。AcSDKP处理大鼠心脏成纤维细胞的流式细胞术显示，AcSDKP显著抑制细胞周期从G0/G1期向S期的进展。在转染smad敏感荧光素酶报告结构的心脏成纤维细胞中，AcSDKP使荧光素酶活性降低55±9.7% (P =0.01)。此外，在AcSDKP处理的心脏成纤维细胞中，Smad2的磷酸化和核易位降低。综上所述，AcSDKP抑制心脏成纤维细胞的生长，也抑制TGF&bgr;1刺激的Smad2磷酸化。由于AcSDKP在ACE抑制剂治疗期间显著增加，这表明ACE抑制剂可以抑制心脏纤维化，这是一种独立于血管紧张素II的新途径。
{"title":"N-Acetyl-Ser-Asp-Lys-Pro Inhibits Phosphorylation of Smad2 in Cardiac Fibroblasts","authors":"S. Pokharel, S. Rasoul, A. Roks, R. V. van Leeuwen, M. V. van Luyn, L. Deelman, J. Smits, O. Carretero, W. V. van Gilst, Y. Pinto","doi":"10.1161/01.HYP.0000025880.56816.FA","DOIUrl":"https://doi.org/10.1161/01.HYP.0000025880.56816.FA","url":null,"abstract":"N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a specific substrate for the N-terminal site of ACE and increases 5-fold during ACE inhibitor therapy. It is known to inhibit the proliferation of hematopoietic stem cells and has also recently been reported to inhibit the growth of cardiac fibroblasts. We investigated its mode of action in cardiac fibroblasts by assessing its influence on transforming growth factor &bgr;1 (TGF&bgr;1)–mediated Smad signaling. AcSDKP inhibited the proliferation of isolated cardiac fibroblasts (P <0.05) but significantly stimulated the proliferation of vascular smooth muscle cells. Flow cytometry of rat cardiac fibroblasts treated with AcSDKP showed significant inhibition of the progression of cells from G0/G1 phase to S phase of the cell cycle. In cardiac fibroblasts transfected with a Smad-sensitive luciferase reporter construct, AcSDKP decreased luciferase activity by 55±9.7% (P =0.01). Moreover, phosphorylation and nuclear translocation of Smad2 was decreased in cardiac fibroblasts treated with AcSDKP. To conclude, AcSDKP inhibits the growth of cardiac fibroblasts and also inhibits TGF&bgr;1-stimulated phosphorylation of Smad2. Because AcSDKP increases substantially during ACE inhibitor therapy, this suggests a novel pathway independent of angiotensin II, by which ACE inhibitors can inhibit cardiac fibrosis.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"19 1","pages":"155-161"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87867400","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 : 2002-08-01DOI: 10.1161/01.HYP.0000024348.87637.6F
S. Delbosc, J. Cristol, B. Descomps, A. Mimran, B. Jover
The influence of the HMG-CoA reductase inhibitor simvastatin was assessed on the cardiovascular alterations and production of free radicals associated with chronic angiotensin II (Ang II) infusion. Simvastatin (60 mg/kg per day PO) or placebo were given concomitantly for 10 days in Sprague-Dawley rats infused with Ang II (200 ng/kg per minute SC, osmotic pump). In addition, simvastatin or placebo was also given in vehicle-infused rats. Tail-cuff pressure and albuminuria were measured before and at the end of the treatment period. Cardiac weight, carotid structure, production of reactive oxygen species (ROS, by chemiluminescence) by polymorphonuclear leukocytes and aortic wall as well as protein and lipid oxidation products were determined at the end of the study. Ang II increased tail-cuff pressure by 56±12 mm Hg and simvastatin blunted the development of hypertension by ≈70% (19±5 mm Hg). Increases in heart weight index and carotid cross-sectional area induced by Ang II were obliterated by simvastatin (3.18±0.09 versus 3.46±0.11 mg/g body wt and 0.125±0.010 versus 0.177±0.010 mm2, respectively). The Ang II–induced increases in leukocyte and aortic production of ROS as well as protein and lipid oxidation products were prevented by simvastatin. No effect of simvastatin was detected in non–Ang II–infused rats. These results indicate that simvastatin prevented the development of hypertension and cardiovascular hypertrophy together with inhibition of the induced angiotensin II production of ROS. Therefore, inhibition of HMG CoA reductase by statins may have a beneficial effect on cardiovascular alterations through its antioxidant action in experimental Ang II–dependent hypertension.
评估HMG-CoA还原酶抑制剂辛伐他汀对慢性血管紧张素II (Ang II)输注相关的心血管改变和自由基产生的影响。在Sprague-Dawley大鼠注射Ang II (200 ng/kg / min SC，渗透泵)后，同时给予辛伐他汀(60 mg/kg / day PO)或安慰剂10天。此外，还给辛伐他汀或安慰剂给药。在治疗前和治疗结束时测量尾袖压和蛋白尿。在研究结束时测定心脏重量、颈动脉结构、多形核白细胞和主动脉壁产生的活性氧(ROS，通过化学发光)以及蛋白质和脂质氧化产物。Ang II使尾袖压升高56±12 mm Hg，辛伐他汀使高血压的发展钝化约70%(19±5 mm Hg)。辛伐他汀可消除Angⅱ引起的心脏重量指数和颈动脉横截面积的增加(分别为3.18±0.09对3.46±0.11 mg/g体重量，0.125±0.010对0.177±0.010 mm2)。辛伐他汀可以防止Ang ii诱导的白细胞和主动脉ROS生成的增加以及蛋白质和脂质氧化产物的增加。辛伐他汀对未注射angii的大鼠无影响。这些结果表明，辛伐他汀可以预防高血压和心血管肥大的发生，并抑制诱导的血管紧张素II的生成。因此，他汀类药物抑制HMG辅酶a还原酶可能通过其抗氧化作用对实验性angii依赖性高血压的心血管改变产生有益影响。
{"title":"Simvastatin Prevents Angiotensin II–Induced Cardiac Alteration and Oxidative Stress","authors":"S. Delbosc, J. Cristol, B. Descomps, A. Mimran, B. Jover","doi":"10.1161/01.HYP.0000024348.87637.6F","DOIUrl":"https://doi.org/10.1161/01.HYP.0000024348.87637.6F","url":null,"abstract":"The influence of the HMG-CoA reductase inhibitor simvastatin was assessed on the cardiovascular alterations and production of free radicals associated with chronic angiotensin II (Ang II) infusion. Simvastatin (60 mg/kg per day PO) or placebo were given concomitantly for 10 days in Sprague-Dawley rats infused with Ang II (200 ng/kg per minute SC, osmotic pump). In addition, simvastatin or placebo was also given in vehicle-infused rats. Tail-cuff pressure and albuminuria were measured before and at the end of the treatment period. Cardiac weight, carotid structure, production of reactive oxygen species (ROS, by chemiluminescence) by polymorphonuclear leukocytes and aortic wall as well as protein and lipid oxidation products were determined at the end of the study. Ang II increased tail-cuff pressure by 56±12 mm Hg and simvastatin blunted the development of hypertension by ≈70% (19±5 mm Hg). Increases in heart weight index and carotid cross-sectional area induced by Ang II were obliterated by simvastatin (3.18±0.09 versus 3.46±0.11 mg/g body wt and 0.125±0.010 versus 0.177±0.010 mm2, respectively). The Ang II–induced increases in leukocyte and aortic production of ROS as well as protein and lipid oxidation products were prevented by simvastatin. No effect of simvastatin was detected in non–Ang II–infused rats. These results indicate that simvastatin prevented the development of hypertension and cardiovascular hypertrophy together with inhibition of the induced angiotensin II production of ROS. Therefore, inhibition of HMG CoA reductase by statins may have a beneficial effect on cardiovascular alterations through its antioxidant action in experimental Ang II–dependent hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"1 1","pages":"142-147"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88272937","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 : 2002-08-01DOI: 10.1161/01.HYP.0000027134.14160.1D
B. Parhami-Seren, R. Haberly, M. N. Margolies, G. T. Haupert
Conservation of the binding site on mammalian Na+,K+-ATPase for cardiac glycosides and the importance of the Na+ pump in mammalian cellular physiology has stimulated the search for a mammalian analog of these plant compounds. One candidate, isolated from brain and blood, appears to be ouabain itself or a closely related isomer, the ouabain-like compound. Little is known about the circulating form. Because human steroid hormones circulate with carrier proteins, we produced a ouabain-specific monoclonal antibody (mAb 1-10) and used it to probe normal human plasma for ouabain-protein carrier complex. Ouabain-like biological activity was isolated in association with protein bands of 80, 50, and 25 kDa. These proteins appear to be human immunoglobulins or immunoglobulin-like because they are recognized by anti-human immunoglobulin antibodies, but not by anti-mouse immunoglobulin antibodies. The protein-containing fractions inhibit the binding of mAb 1-10 to immobilized ouabain, and with further purification on protein A, the immunoglobulin-like protein binds radioactive ouabain with an IC50 of 200 to 600 nmol/L, but binds digoxin with 100-fold less affinity, suggesting specificity for ouabain or its isomer. Active protein fractions after purification on C18 inhibit Na+ pump activity in human erythrocytes (IC50≈4 nmol/L, ouabain equivalents), and this chromatography appears to dissociate the ouabain-like compound from the immunoglobulin protein(s). These immunoglobulin-like molecules may represent a subset of immunoglobulins (≤0.5% of total protein A immunoglobulin) that function as a reservoir and delivery system for ouabain-like compounds in the modulation of human Na+, K+-ATPase in vivo.
{"title":"Ouabain-Binding Protein(s) From Human Plasma","authors":"B. Parhami-Seren, R. Haberly, M. N. Margolies, G. T. Haupert","doi":"10.1161/01.HYP.0000027134.14160.1D","DOIUrl":"https://doi.org/10.1161/01.HYP.0000027134.14160.1D","url":null,"abstract":"Conservation of the binding site on mammalian Na+,K+-ATPase for cardiac glycosides and the importance of the Na+ pump in mammalian cellular physiology has stimulated the search for a mammalian analog of these plant compounds. One candidate, isolated from brain and blood, appears to be ouabain itself or a closely related isomer, the ouabain-like compound. Little is known about the circulating form. Because human steroid hormones circulate with carrier proteins, we produced a ouabain-specific monoclonal antibody (mAb 1-10) and used it to probe normal human plasma for ouabain-protein carrier complex. Ouabain-like biological activity was isolated in association with protein bands of 80, 50, and 25 kDa. These proteins appear to be human immunoglobulins or immunoglobulin-like because they are recognized by anti-human immunoglobulin antibodies, but not by anti-mouse immunoglobulin antibodies. The protein-containing fractions inhibit the binding of mAb 1-10 to immobilized ouabain, and with further purification on protein A, the immunoglobulin-like protein binds radioactive ouabain with an IC50 of 200 to 600 nmol/L, but binds digoxin with 100-fold less affinity, suggesting specificity for ouabain or its isomer. Active protein fractions after purification on C18 inhibit Na+ pump activity in human erythrocytes (IC50≈4 nmol/L, ouabain equivalents), and this chromatography appears to dissociate the ouabain-like compound from the immunoglobulin protein(s). These immunoglobulin-like molecules may represent a subset of immunoglobulins (≤0.5% of total protein A immunoglobulin) that function as a reservoir and delivery system for ouabain-like compounds in the modulation of human Na+, K+-ATPase in vivo.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"4 1","pages":"220-228"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89200005","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 : 2002-08-01DOI: 10.1161/01.HYP.0000026809.68674.F9
S. Vanni, G. Polidori, I. Cecioni, S. Serni, M. Carini, P. Modesti
Renal endothelin-1 participates in sodium and water handling, and its urinary excretion is increased in sodium-retentive states. We compared the cortical and medullary renal expression of prepro-endothelin-1, endothelin-converting enzyme-1, and endothelin type A and type B receptors in patients who underwent nephrectomy after normal (108 mmol/d NaCl; n=6) or low (20 mmol/d NaCl; n=6) sodium diet and investigated whether sodium exerts a direct role on endothelin receptor binding in vitro. With normal sodium diet prepro-endothelin-1 mRNA was 3-fold higher in renal medulla than in cortex (P <0.01), whereas endothelin-converting enzyme-1 mRNA was equally distributed. Endothelin-1 receptor density was 2-fold higher in renal medulla than in cortex (P <0.05). Type B was the main receptor subtype in both regions. In the renal cortex, low sodium diet caused a 194% increase in prepro-endothelin-1 mRNA (P <0.05), whereas endothelin-converting enzyme-1 type B and type A receptors remained unchanged. In contrast, in the renal medulla the increase in prepro-endothelin-1 mRNA (+30%, P <0.05) was associated with a selective increase in type B receptor for both mRNA expression (+37%, P <0.05) and binding density (+55%, P <0.05). Increasing in vitro sodium concentrations between 154 and 308 mmol/L significantly enhanced type B receptor density (P <0.05) and affinity (P <0.05). In conclusion, during low sodium diet, renal prepro-endothelin-1 synthesis increases mainly in the renal cortex (where no changes in receptors occur), whereas type B receptor is selectively enhanced in the renal medulla. The range of sodium concentrations that are physiologically present in vivo in the renal medulla selectively modulate type B receptor density and affinity.
{"title":"ETB Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake","authors":"S. Vanni, G. Polidori, I. Cecioni, S. Serni, M. Carini, P. Modesti","doi":"10.1161/01.HYP.0000026809.68674.F9","DOIUrl":"https://doi.org/10.1161/01.HYP.0000026809.68674.F9","url":null,"abstract":"Renal endothelin-1 participates in sodium and water handling, and its urinary excretion is increased in sodium-retentive states. We compared the cortical and medullary renal expression of prepro-endothelin-1, endothelin-converting enzyme-1, and endothelin type A and type B receptors in patients who underwent nephrectomy after normal (108 mmol/d NaCl; n=6) or low (20 mmol/d NaCl; n=6) sodium diet and investigated whether sodium exerts a direct role on endothelin receptor binding in vitro. With normal sodium diet prepro-endothelin-1 mRNA was 3-fold higher in renal medulla than in cortex (P <0.01), whereas endothelin-converting enzyme-1 mRNA was equally distributed. Endothelin-1 receptor density was 2-fold higher in renal medulla than in cortex (P <0.05). Type B was the main receptor subtype in both regions. In the renal cortex, low sodium diet caused a 194% increase in prepro-endothelin-1 mRNA (P <0.05), whereas endothelin-converting enzyme-1 type B and type A receptors remained unchanged. In contrast, in the renal medulla the increase in prepro-endothelin-1 mRNA (+30%, P <0.05) was associated with a selective increase in type B receptor for both mRNA expression (+37%, P <0.05) and binding density (+55%, P <0.05). Increasing in vitro sodium concentrations between 154 and 308 mmol/L significantly enhanced type B receptor density (P <0.05) and affinity (P <0.05). In conclusion, during low sodium diet, renal prepro-endothelin-1 synthesis increases mainly in the renal cortex (where no changes in receptors occur), whereas type B receptor is selectively enhanced in the renal medulla. The range of sodium concentrations that are physiologically present in vivo in the renal medulla selectively modulate type B receptor density and affinity.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"210 1","pages":"179-185"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77490966","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 : 2002-08-01DOI: 10.1161/01.HYP.0000024573.17293.23
M. Lindsay, P. Maxwell, F. Dunn
This study was designed to document noninvasively the pathological mechanisms responsible for myocardial fibrosis and to assess the clinical utility of plasma markers of collagen synthesis and degradation as screening tools for the assessment of fibrosis in hypertension. We studied 100 never-treated hypertensive patients and 50 normal subjects. Echocardiographic assessment was made of left ventricular (LV) mass and diastolic filling using measurement of E:A ratio, E wave deceleration time (E dec), and isovolumic relaxation time (IVRT). The presence of diastolic dysfunction was taken as a surrogate marker for the presence of myocardial fibrosis. Plasma carboxy-terminal propeptide of collagen type I (PICP), carboxy-terminal telopeptide of collagen type I (CITP), and tissue inhibitor of matrix metalloproteinases type I (TIMP-1) were measured as markers of collagen synthesis, degradation, and inhibition of degradation, respectively. Plasma TIMP-1 was significantly elevated in the hypertensive cohort (358 ng/mL versus 253 ng/mL, P <0.001) as were CITP (5.2 &mgr;g/L versus 2.9 &mgr;g/L, P <0.001), and PICP (200 &mgr;g/L versus 166 &mgr;g/L, P <0.05). TIMP-1 was significantly elevated in patients with diastolic dysfunction (421 ng/mL versus 283 ng/mL P <0.01) and correlated with markers of diastolic filling, namely E:A ratio (r =0.26, P <0.05) and E Dec (r =0.41, P <0.01). A plasma TIMP-1 level of >500 ng/mL had a specificity of 97% and a positive predictive value of 96% in predicting diastolic dysfunction. In patients with untreated hypertension, there is evidence of increased collagen synthesis, degradation, and inhibition of degradation resulting in fibrosis. Our results demonstrate that plasma TIMP-1 correlates with markers of LV diastolic filling, is predictive of LV dysfunction, and is a potential noninvasive marker of fibrosis.
本研究旨在无创记录心肌纤维化的病理机制，并评估血浆胶原合成和降解标志物作为评估高血压纤维化筛查工具的临床应用。我们研究了100例从未治疗过的高血压患者和50例正常人。超声心动图评价左室(LV)质量和舒张充盈，测量E:A比、E波减速时间(E dec)和等容松弛时间(IVRT)。舒张功能障碍的存在被作为心肌纤维化存在的替代标志。分别测定血浆I型胶原羧基末端前肽(PICP)、I型胶原羧基末端末端肽(CITP)和I型基质金属蛋白酶组织抑制剂(TIMP-1)作为胶原合成、降解和降解抑制的标志物。血浆TIMP-1在高血压队列中显著升高(358 ng/mL vs 253 ng/mL, p500 ng/mL在预测舒张功能障碍方面特异性为97%，阳性预测值为96%。在未经治疗的高血压患者中，有证据表明胶原合成、降解和降解抑制增加导致纤维化。我们的研究结果表明，血浆TIMP-1与左室舒张充盈标志物相关，可预测左室功能障碍，并且是潜在的无创纤维化标志物。
{"title":"TIMP-1: A Marker of Left Ventricular Diastolic Dysfunction and Fibrosis in Hypertension","authors":"M. Lindsay, P. Maxwell, F. Dunn","doi":"10.1161/01.HYP.0000024573.17293.23","DOIUrl":"https://doi.org/10.1161/01.HYP.0000024573.17293.23","url":null,"abstract":"This study was designed to document noninvasively the pathological mechanisms responsible for myocardial fibrosis and to assess the clinical utility of plasma markers of collagen synthesis and degradation as screening tools for the assessment of fibrosis in hypertension. We studied 100 never-treated hypertensive patients and 50 normal subjects. Echocardiographic assessment was made of left ventricular (LV) mass and diastolic filling using measurement of E:A ratio, E wave deceleration time (E dec), and isovolumic relaxation time (IVRT). The presence of diastolic dysfunction was taken as a surrogate marker for the presence of myocardial fibrosis. Plasma carboxy-terminal propeptide of collagen type I (PICP), carboxy-terminal telopeptide of collagen type I (CITP), and tissue inhibitor of matrix metalloproteinases type I (TIMP-1) were measured as markers of collagen synthesis, degradation, and inhibition of degradation, respectively. Plasma TIMP-1 was significantly elevated in the hypertensive cohort (358 ng/mL versus 253 ng/mL, P <0.001) as were CITP (5.2 &mgr;g/L versus 2.9 &mgr;g/L, P <0.001), and PICP (200 &mgr;g/L versus 166 &mgr;g/L, P <0.05). TIMP-1 was significantly elevated in patients with diastolic dysfunction (421 ng/mL versus 283 ng/mL P <0.01) and correlated with markers of diastolic filling, namely E:A ratio (r =0.26, P <0.05) and E Dec (r =0.41, P <0.01). A plasma TIMP-1 level of >500 ng/mL had a specificity of 97% and a positive predictive value of 96% in predicting diastolic dysfunction. In patients with untreated hypertension, there is evidence of increased collagen synthesis, degradation, and inhibition of degradation resulting in fibrosis. Our results demonstrate that plasma TIMP-1 correlates with markers of LV diastolic filling, is predictive of LV dysfunction, and is a potential noninvasive marker of fibrosis.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"24 1","pages":"136-141"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77848735","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 : 2002-08-01DOI: 10.1161/01.HYP.0000025441.06473.89
M. Slama, D. Sušić, J. Varagić, E. Frohlich
In 1979, we first reported occurrence of biventricular hypertrophy in the original normotensive Wistar-Kyoto (WKY) strain obtained from the National Heart, Lung, and Blood Institute, which was derived directly from the Kyoto laboratory of Okamoto. At that time, we recommended that both ventricles be weighted when WKY are studied so that invalid conclusions are not made. Because no paper confirmed these findings for almost 20 years, heart weights were reported in only a few WKY studies, and the cause of this biventricular hypertrophy remained unknown, we re-evaluated this problem in commercially available rats. We, therefore, investigated WKY rats using transthoracic echocardiography to define the congenital heart defect. Up to 28% of commercially available WKY rats demonstrated severe congenital cardiac abnormalities associated with biventricular hypertrophy. Ventricular septal defect with pulmonary regurgitation was the most commonly encountered cardiac defect; other abnormalities included patent ductus arteriosus, and valvular defects. Pathologic and invasive hemodynamic studies confirmed these echocardiographic findings. Because this defect occurs in a large number of WKY rats obtained commercially from 2 different sources, investigators using this strain must carefully measure both ventricular weights to be certain that inappropriate and invalid conclusions are not derived therefrom.
{"title":"High Rate of Ventricular Septal Defects in WKY Rats","authors":"M. Slama, D. Sušić, J. Varagić, E. Frohlich","doi":"10.1161/01.HYP.0000025441.06473.89","DOIUrl":"https://doi.org/10.1161/01.HYP.0000025441.06473.89","url":null,"abstract":"In 1979, we first reported occurrence of biventricular hypertrophy in the original normotensive Wistar-Kyoto (WKY) strain obtained from the National Heart, Lung, and Blood Institute, which was derived directly from the Kyoto laboratory of Okamoto. At that time, we recommended that both ventricles be weighted when WKY are studied so that invalid conclusions are not made. Because no paper confirmed these findings for almost 20 years, heart weights were reported in only a few WKY studies, and the cause of this biventricular hypertrophy remained unknown, we re-evaluated this problem in commercially available rats. We, therefore, investigated WKY rats using transthoracic echocardiography to define the congenital heart defect. Up to 28% of commercially available WKY rats demonstrated severe congenital cardiac abnormalities associated with biventricular hypertrophy. Ventricular septal defect with pulmonary regurgitation was the most commonly encountered cardiac defect; other abnormalities included patent ductus arteriosus, and valvular defects. Pathologic and invasive hemodynamic studies confirmed these echocardiographic findings. Because this defect occurs in a large number of WKY rats obtained commercially from 2 different sources, investigators using this strain must carefully measure both ventricular weights to be certain that inappropriate and invalid conclusions are not derived therefrom.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"15 1","pages":"175-178"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76497865","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 : 2002-08-01DOI: 10.1161/01.HYP.0000024218.04872.F3
C. McEniery, I. Wilkinson, D. Jenkins, D. Webb
Essential hypertension is a common disorder, associated with increased endothelin-1–mediated vasoconstrictor tone at rest. We hypothesized that increased vasoconstrictor activity of endothelin-1 might explain why the normal decrease in peripheral vascular resistance in response to exercise is attenuated in hypertensive patients. Therefore, we investigated the effect of endothelin A (ETA) receptor blockade on the vasodilator response to handgrip exercise. Forearm blood flow responses to handgrip exercise (15%, 30%, and 45% of maximum voluntary contraction) were assessed in hypertensive patients and matched normotensive subjects, before and after intra-arterial infusions of the ETA receptor antagonist BQ-123; a control dilator, hydralazine; and placebo (saline). Preinfusion (baseline) vasodilation in response to exercise was significantly attenuated at each workload in hypertensive patients compared with normotensive subjects. Intra-arterial infusions of hydralazine and saline did not increase the vasodilator response to exercise in either hypertensives or normotensives at any workload. The vasodilator response to exercise was markedly enhanced after BQ-123 at the 2 higher workloads in hypertensives (157±48%, P <0.01; 203±58%, P <0.01) but not in normotensives. This suggests that the impaired vasodilator response to exercise in hypertensive patients is, at least in part, a functional limitation caused by endogenous ETA receptor–mediated vasoconstriction. Treatment with endothelin receptor antagonists may, therefore, increase exercise capacity in essential hypertension.
{"title":"Endogenous Endothelin-1 Limits Exercise-Induced Vasodilation in Hypertensive Humans","authors":"C. McEniery, I. Wilkinson, D. Jenkins, D. Webb","doi":"10.1161/01.HYP.0000024218.04872.F3","DOIUrl":"https://doi.org/10.1161/01.HYP.0000024218.04872.F3","url":null,"abstract":"Essential hypertension is a common disorder, associated with increased endothelin-1–mediated vasoconstrictor tone at rest. We hypothesized that increased vasoconstrictor activity of endothelin-1 might explain why the normal decrease in peripheral vascular resistance in response to exercise is attenuated in hypertensive patients. Therefore, we investigated the effect of endothelin A (ETA) receptor blockade on the vasodilator response to handgrip exercise. Forearm blood flow responses to handgrip exercise (15%, 30%, and 45% of maximum voluntary contraction) were assessed in hypertensive patients and matched normotensive subjects, before and after intra-arterial infusions of the ETA receptor antagonist BQ-123; a control dilator, hydralazine; and placebo (saline). Preinfusion (baseline) vasodilation in response to exercise was significantly attenuated at each workload in hypertensive patients compared with normotensive subjects. Intra-arterial infusions of hydralazine and saline did not increase the vasodilator response to exercise in either hypertensives or normotensives at any workload. The vasodilator response to exercise was markedly enhanced after BQ-123 at the 2 higher workloads in hypertensives (157±48%, P <0.01; 203±58%, P <0.01) but not in normotensives. This suggests that the impaired vasodilator response to exercise in hypertensive patients is, at least in part, a functional limitation caused by endogenous ETA receptor–mediated vasoconstriction. Treatment with endothelin receptor antagonists may, therefore, increase exercise capacity in essential hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"39 1","pages":"202-206"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79195358","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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