Hypertension: Journal of the American Heart Association最新文献_第3页

Differential Regulation of Elevated Renal Angiotensin II in Chronic Renal Ischemia 慢性肾缺血中肾血管紧张素II升高的差异调控

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022060.13995.ED

H. Tokuyama, K. Hayashi, H. Matsuda, E. Kubota, M. Honda, K. Okubo, I. Takamatsu, S. Tatematsu, Y. Ozawa, S. Wakino, T. Saruta

{"title":"Differential Regulation of Elevated Renal Angiotensin II in Chronic Renal Ischemia","authors":"H. Tokuyama, K. Hayashi, H. Matsuda, E. Kubota, M. Honda, K. Okubo, I. Takamatsu, S. Tatematsu, Y. Ozawa, S. Wakino, T. Saruta","doi":"10.1161/01.HYP.0000022060.13995.ED","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022060.13995.ED","url":null,"abstract":"The present study was undertaken to clarify the role of intrarenal angiotensin (Ang) II and its generating pathways in clipped and nonclipped kidneys of 4-week unilateral renal artery stenosis in anesthetized dogs. After 4 weeks, renal plasma flow (RPF) decreased in clipped and nonclipped kidneys (baseline, 59±3; clipped, 16±1; nonclipped, 44±2 mL/min;P <0.01, n=22). Renal Ang I levels increased only in clipped, whereas intrarenal Ang II contents were elevated in both clipped (from 0.7±0.1 to 2.0±0.2 pg/mg tissue) and nonclipped kidneys (from 0.6±0.1 to 2.5±0.3 pg/mg tissue). Intrarenal ACE activity was increased in nonclipped kidneys but was unaltered in clipped kidneys. An angiotensin receptor antagonist (olmesartan medoxomil) given into the renal artery markedly restored RPF, and dilated both afferent and efferent arterioles (using intravital videomicroscopy). Furthermore, in clipped kidneys, the elevated Ang II was suppressed by a chymase inhibitor, chymostatin (from 2.1±0.6 to 0.8±0.1 pg/mg tissue;P <0.05), but not by cilazaprilat. In nonclipped kidneys, in contrast, cilazaprilat, but not chymostatin, potently inhibited the intrarenal Ang II generation (from 2.4±0.3 to 1.5±0.2 pg/mg tissue;P <0.05). Finally, [Pro11-d-Ala12]Ang I (an inactive precursor that yields Ang II by chymase but not by ACE; 1 to 50 nmol/kg) markedly elevated intrarenal Ang II in clipped, but not in nonclipped, kidneys. In conclusion, renal Ang II contents were elevated in both clipped and nonclipped kidneys, which contributed to the altered renal hemodynamics and microvascular tone. Furthermore, the mechanisms for intrarenal Ang II generation differ, and chymase activity is enhanced in clipped kidneys, whereas ACE-mediated Ang II generation is possibly responsible for elevated Ang II contents in nonclipped kidneys.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"16 1","pages":"34-40"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86444867","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}

引用次数: 49

Amiloride, a Specific Drug for Hypertension in Black People With T594M Variant? 阿米洛利是黑人T594M变异高血压的特效药吗?

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022570.02119.75

E. Baker, A. Duggal, Yanbin Dong, Nicola J. Ireson, M. Wood, N. Markandu, G. MacGregor

{"title":"Amiloride, a Specific Drug for Hypertension in Black People With T594M Variant?","authors":"E. Baker, A. Duggal, Yanbin Dong, Nicola J. Ireson, M. Wood, N. Markandu, G. MacGregor","doi":"10.1161/01.HYP.0000022570.02119.75","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022570.02119.75","url":null,"abstract":"The T594M polymorphism of the epithelial sodium channel is found in ≈5% of people of African origin and is significantly associated with high blood pressure. Although the T594M polymorphism could increase renal sodium absorption through affected channels, it is not known whether this polymorphism causes hypertension. Amiloride specifically inhibits overactive sodium channels and effectively controls blood pressure in Liddle’s syndrome, in which hypertension is caused by separate epithelial sodium channel mutations. The aim of this study was to determine whether amiloride was effective in lowering blood pressure in individuals with the T594M polymorphism. In an open, controlled study, 14 black hypertensive individuals with the T594M polymorphism were withdrawn from their usual medication and treated with amiloride. On entry to the study, individuals taking a mean of 2 drugs had blood pressure of 142/89±3/3 mm Hg. Amiloride alone (10 mg BID) controlled blood pressure effectively to the same level (140/91±4/2 mm Hg). When amiloride was withdrawn for 2 weeks, there was a large increase in blood pressure of 17/8±4/2 mm Hg (systolic, P <0.05; diastolic, P <0.01). On restarting amiloride, blood pressure was again controlled to 140/88±6/2 mm Hg. These results demonstrate that 10 mg BID amiloride is effective in controlling blood pressure in hypertensive individuals of African origin who have the T594M polymorphism. Our study supports the concept that the T594M polymorphism contributes to the elevation of blood pressure and suggests that consideration should be given to the use of amiloride in affected individuals.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"5 1","pages":"13-17"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85590814","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}

引用次数: 95

Cardiovascular Phenotypes of Kinin B2 Receptor– and Tissue Kallikrein–Deficient Mice 激肽B2受体和组织激肽缺乏小鼠的心血管表型

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000021747.43346.95

F. Trabold, S. Pons, A. Hagège, M. Bloch-Faure, F. Alhenc-Gelas, J. Giudicelli, Christine Richer-Giudicelli, P. Meneton

{"title":"Cardiovascular Phenotypes of Kinin B2 Receptor– and Tissue Kallikrein–Deficient Mice","authors":"F. Trabold, S. Pons, A. Hagège, M. Bloch-Faure, F. Alhenc-Gelas, J. Giudicelli, Christine Richer-Giudicelli, P. Meneton","doi":"10.1161/01.HYP.0000021747.43346.95","DOIUrl":"https://doi.org/10.1161/01.HYP.0000021747.43346.95","url":null,"abstract":"To clarify the role of the kallikrein-kinin system in cardiovascular homeostasis, the systemic and regional hemodynamics of kinin B2 receptor–deficient (B2−/−) and tissue kallikrein–deficient (TK−/−) mice were compared with their wild-type (WT) littermates on a pure C57BL/6 genetic background. B2−/−, TK−/−, and WT adult mice were normotensive and displayed normal hemodynamic (left ventricular [LV] pressure, cardiac output, total peripheral resistance, dP/dtmax) and echocardiographic (septum and LV posterior wall thickness, LV diameter, LV mass, and LV fractional shortening) parameters. However, heart rate was lower in B2−/− mice compared with TK−/− and WT mice. In addition, B2−/− mice, but not TK−/− mice, exhibited lower coronary and renal blood flows and greater corresponding vascular resistances than did WT mice, indicating a tonic physiological vasodilating effect of bradykinin in these vascular beds. However, maximal coronary vasodilatation capacity, estimated after dipyridamole infusion, was similar in the 3 groups of mice. B2−/− mice were significantly more sensitive than were TK−/− mice to the vasoconstrictor effects of angiotensin II and norepinephrine. Finally, renin mRNA levels were significantly greater in B2−/− mice and smaller in TK−/− mice compared with WT mice. Taken together, these results indicate that under basal conditions, the kinin B2 receptor is not an important determinant of blood pressure in mice but is involved in the control of regional vascular tone in the coronaries and the kidneys. The phenotypic differences observed between TK−/− and B2−/− mice could be underlain by tissue kallikrein kinin–independent effect and/or kinin B1 receptor activation.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"23 1","pages":"90-95"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82515704","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}

引用次数: 80

Brain Sodium Channels Mediate Increases in Brain “Ouabain” and Blood Pressure in Dahl S Rats 脑钠通道介导达尔S大鼠脑“瓦巴因”和血压升高

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022659.17774.E4

Hao Wang, F. Leenen

{"title":"Brain Sodium Channels Mediate Increases in Brain “Ouabain” and Blood Pressure in Dahl S Rats","authors":"Hao Wang, F. Leenen","doi":"10.1161/01.HYP.0000022659.17774.E4","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022659.17774.E4","url":null,"abstract":"Central infusions of benzamil prevent/reverse salt-induced hypertension in genetic models of salt-sensitive hypertension. Benzamil acts by blockade of ion—presumably sodium—channels. In the present study, we assessed in Dahl salt-sensitive (S) rats on high salt intake whether these channels mediate increases in brain “ouabain” and, thereby, hypertension. Intracerebroventricular (icv) infusions of a low (1.2 &mgr;g/kg per hour) or high (4.0 &mgr;g/kg per hour) dose of benzamil were given to Dahl S rats on high salt diet (1370 &mgr;mol Na+/g food) for 2 or 4 weeks. “Ouabain” content was measured using a specific enzyme-linked immunosorbent assay (ELISA). Systolic blood pressure (BP) in Dahl S rats on high salt for 4 weeks increased markedly (188±10 versus 128±4 mm Hg, n=8, P <0.05). Benzamil fully blocked this increase (131±7 mm Hg after the high dose of benzamil). Hypothalamic and pituitary “ouabain” increased significantly (22±7 versus 12±3 and 151±38 versus 69±6 ng/g tissue, respectively, P <0.05) in Dahl S rats on high salt versus regular salt diet for 2 weeks. Benzamil blocked these increases of brain “ouabain” to high salt intake. Similarly, high salt intake for 4 weeks increased hypothalamic (18±2 versus 13±1 ng/g tissue, P <0.05) and pituitary (183±30 versus 78±8 ng/g tissue, P <0.05) “ouabain.” Benzamil also inhibited these increases of brain “ouabain.” Both hypothalamic and pituitary “ouabain” showed significant positive correlations with BP. In contrast, high salt intake did not affect “ouabain” levels in the adrenal gland or plasma in Dahl S rats on high salt for either 2 or 4 weeks. These findings indicate that in Dahl S rats high salt intake only increases brain and not peripheral “ouabain” and that benzamil-blockable brain sodium channels mediate the increases in brain “ouabain” and the subsequent hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"8 1","pages":"96-100"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78877887","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}

引用次数: 69

Genome Scans for Blood Pressure and Hypertension: The National Heart, Lung, and Blood Institute Family Heart Study* 基因组扫描血压和高血压:国家心脏、肺和血液研究所家庭心脏研究*

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022660.28915.B1

Steven C. Hunt, R. C. Ellison, Larry D. Atwood, J. Pankow, Michael A. Province, Mark F. Leppert

{"title":"Genome Scans for Blood Pressure and Hypertension: The National Heart, Lung, and Blood Institute Family Heart Study*","authors":"Steven C. Hunt, R. C. Ellison, Larry D. Atwood, J. Pankow, Michael A. Province, Mark F. Leppert","doi":"10.1161/01.HYP.0000022660.28915.B1","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022660.28915.B1","url":null,"abstract":"This study presents genome scans for hypertension and blood pressures from 2959 individuals in 500 white families from the National Heart, Lung, and Blood Institute Family Heart Study. Genome scans were performed with different methods of handling the 27% of individuals taking antihypertensive medications. Variance components LOD scores were estimated by assigning medicated hypertensive individuals (1) to have a blood pressure of 140/90; (2) to be missing; and (3) to have a randomly assigned systolic blood pressure between 140 and 160 (N[150,5] distribution) and diastolic blood pressure between 90 and 100 mm Hg (N[95,2.5] distribution). There were 5 regions with heterogeneity LOD scores ≥2.0 for hypertension (unadjusted for multiple models): 2.8 on chromosome 1 (192 cM), 2.6 on chromosome 7 (58 cM), 2.0 on chromosome 7 (127 cM), 2.4 on chromosome 12 (83 cM), and 2.4 on chromosome 15 (103 cM). Diastolic blood pressure had no LOD scores ≥2.0. Only chromosome 6 showed linkage for systolic blood pressure, with a LOD score of 3.3 at 88.7 cM from the initial randomization. Multiple randomizations of medicated subjects’ systolic blood pressures yielded a mean LOD score of 2.8±0.4, whereas setting medicated systolic blood pressures to 140 mm Hg yielded a LOD score of 3.3. Excluding the medicated individuals or using their treated blood pressures reduced the LOD scores to 0.8 and 1.3, respectively, indicating the importance of including the extremes of quantitative trait distributions in linkage analyses. These results overlap other published scans, particularly regions on chromosomes 1 and 6, which have been implicated in familial combined hyperlipidemia.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"30 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83384586","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}

引用次数: 124

Norepinephrine and Concentric Hypertrophy in Patients With End-Stage Renal Disease 去甲肾上腺素与终末期肾病患者同心性肥厚的关系

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022063.50739.60

C. Zoccali, F. Mallamaci, G. Tripepi, S. Parlongo, S. Cutrupi, F. Benedetto, A. Cataliotti, L. Malatino

{"title":"Norepinephrine and Concentric Hypertrophy in Patients With End-Stage Renal Disease","authors":"C. Zoccali, F. Mallamaci, G. Tripepi, S. Parlongo, S. Cutrupi, F. Benedetto, A. Cataliotti, L. Malatino","doi":"10.1161/01.HYP.0000022063.50739.60","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022063.50739.60","url":null,"abstract":"We have recently observed that in patients with end-stage renal disease (ESRD) raised plasma norepinephrine (NE) is an independent predictor of incident cardiovascular events but that its prognostic power is reduced when this sympathetic marker is tested in statistical models including also left ventricular mass. Because left ventricular hypertrophy (LVH) may be a mechanism whereby NE contributes to the high rate of cardiovascular events in ESRD, we examined the relationship between plasma NE and echocardiographic parameters of left ventricle mass in a large group of ESRD patients. Mean wall thickness (MWT) was higher in patients in the third NE tertile than in the other 2 tertiles (P =0.001), and such an increase was paralleled by a rise in relative wall thickness (RWT) (P =0.006). Concentric LVH was more prevalent in patients in the third NE tertile (46%) than in the second (38%) and first (25%) NE tertiles. Multivariate regression analysis confirmed that the association of plasma NE with the muscular component of left ventricle (MWT) and with RWT was independent (P ≤0.001) of other cardiovascular risk factors, and in these models, plasma NE ranked as the second correlate of MWT and RWT. Similarly, multiple logistic regression analysis showed that the association of plasma NE with concentric LVH was strong and again independent of other risk factors (P =0.003). Plasma NE is associated to concentric LVH in ESRD patients. These observations constitute a sound basis for testing the effect of anti-adrenergic drugs on left ventricle mass and on cardiovascular outcomes in patients with ESRD.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"22 1","pages":"41-46"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80830333","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}

引用次数: 134

Effects of Hematocrit Changes on Flow-Mediated and Metabolic Vasodilation in Humans 红细胞压积变化对血流介导和代谢性血管舒张的影响

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022571.86090.F3

C. Giannattasio, A. Piperno, M. Failla, A. Vergani, G. Mancia

{"title":"Effects of Hematocrit Changes on Flow-Mediated and Metabolic Vasodilation in Humans","authors":"C. Giannattasio, A. Piperno, M. Failla, A. Vergani, G. Mancia","doi":"10.1161/01.HYP.0000022571.86090.F3","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022571.86090.F3","url":null,"abstract":"Endothelial function is noninvasively assessed by measuring nitric oxide–dependent increase in radial artery diameter accompanying the elevation in shear stress induced by increasing blood flow through a short-lasting ischemia of the hand. However, shear stress also depends on blood viscosity, whose changes might thus affect nitric oxide increase in a manner that is not properly reflected by blood flow changes. In 12 subjects with hemochromatosis, we measured ultrasonographically radial artery diameter and blood flow responses to a 4-minute ischemia of the hand. This was done also after removing 500 mL of blood (and concomitantly infusing 500 mL of saline), which significantly (P <0.01) reduced hemoglobin concentration and hematocrit. The increase in blood flow induced by the 4-minute ischemia was similar before and after blood removal (+76% and +80%), which, in contrast, markedly attenuated the accompanying increase in radial artery diameter (+25% versus +13%, P <0.01). Thus, in humans, blood viscosity is involved in the endothelial response to an increase in shear stress. This implies that this response may not be accurately assessed and compared by quantifying the stimulus only through an increase in blood flow.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"22 1","pages":"74-77"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83788320","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}

引用次数: 41

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats 高盐饮食增强Dahl盐敏感大鼠胰岛素信号传导并诱导胰岛素抵抗

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022880.45113.C9

T. Ogihara, T. Asano, K. Ando, H. Sakoda, M. Anai, N. Shojima, Hiraku Ono, Y. Onishi, M. Fujishiro, Miho Abe, Y. Fukushima, M. Kikuchi, T. Fujita

{"title":"High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats","authors":"T. Ogihara, T. Asano, K. Ando, H. Sakoda, M. Anai, N. Shojima, Hiraku Ono, Y. Onishi, M. Fujishiro, Miho Abe, Y. Fukushima, M. Kikuchi, T. Fujita","doi":"10.1161/01.HYP.0000022880.45113.C9","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022880.45113.C9","url":null,"abstract":"A high-salt diet, which is known to contribute to the pathogenesis of hypertension, is also reportedly associated with insulin resistance. We investigated the effects of a high-salt diet on insulin sensitivity and insulin signaling in salt-sensitive (Dahl-S) and salt resistant (Dahl-R) strains of the Dahl rat. Evaluation of hyperinsulinemic-euglycemic clamp studies and glucose uptake into the isolated soleus muscle revealed that salt loading (8% NaCl) for 4 weeks induced hypertension and significant insulin resistance in Dahl-S rats, whereas no significant effects were observed in Dahl-R rats. Despite the presence of insulin resistance, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrates, activation of phosphatidylinositol 3-kinase, and phosphorylation of Akt were all enhanced in Dahl-S rats fed a high-salt diet. The mechanism underlying this form of insulin resistance thus differs from that previously associated with obesity and dexamethasone and is likely due to the impairment of one or more metabolic steps situated downstream of phosphatidylinositol 3-kinase and Akt activation. Interestingly, supplementation of potassium (8% KCl) ameliorated the changes in insulin sensitivity in Dahl-S rats fed a high-salt diet; this was associated with a slight but significant decrease in blood pressure. Evidence presented suggest that there is an interdependent relationship between insulin sensitivity and salt sensitivity of blood pressure in Dahl-S rats, and it is suggested that supplementing the diet with potassium may exert a protective effect against both hypertension and insulin resistance in salt-sensitive individuals.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"084 1","pages":"83-89"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91158003","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}

引用次数: 152

Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension 普伐他汀对控制良好的高血压患者蛋白尿的影响

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022805.11288.7F

Tsung-Ming Lee, S. Su, Chang‐Her Tsai

{"title":"Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension","authors":"Tsung-Ming Lee, S. Su, Chang‐Her Tsai","doi":"10.1161/01.HYP.0000022805.11288.7F","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022805.11288.7F","url":null,"abstract":"Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effects of 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor (statin) therapy on proteinuria in normolipidemic patients with well-controlled hypertension have not been studied. A total of 63 normolipidemic (total cholesterol <240 mg/dL) and proteinuric (300 to 3000 mg/d) patients with well-controlled blood pressure (<140/90 mm Hg) were randomized to receive either placebo (n=32) or pravastatin (10 mg/d; n=31) after a 3-month placebo period. Pravastatin lowered proteinuria after 6 months by 54% (P <0.0001). Creatinine clearance was stable throughout the study in the 2 groups. Despite unchanged plasma endothelin-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with improvement in urinary protein excretion in pravastatin-treated patients (r =0.64, P =0.001). The urinary excretion of retinol-binding protein decreased after pravastatin administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of IgG did not change significantly throughout the study in either group. Multivariate analysis revealed that proteinuria was only significantly correlated with statin use (P <0.0001, R2= 0.66). Linear regression analysis in the statin-treated group did not show any correlation between changes in lipid profiles and proteinuria regression. Thus, in addition to their primary function of antilipidemia, the addition of pravastatin to treatment for well-controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and lipid-lowering effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"66 1","pages":"67-73"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90061818","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}

引用次数: 133

Aldosterone Breakthrough During Angiotensin II Receptor Antagonist Therapy in Stroke-Prone Spontaneously Hypertensive Rats 血管紧张素II受体拮抗剂治疗卒中易发自发性高血压大鼠醛固酮突破

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000022606.52221.2F

M. Naruse, A. Tanabe, A. Sato, S. Takagi, K. Tsuchiya, T. Imaki, K. Takano

{"title":"Aldosterone Breakthrough During Angiotensin II Receptor Antagonist Therapy in Stroke-Prone Spontaneously Hypertensive Rats","authors":"M. Naruse, A. Tanabe, A. Sato, S. Takagi, K. Tsuchiya, T. Imaki, K. Takano","doi":"10.1161/01.HYP.0000022606.52221.2F","DOIUrl":"https://doi.org/10.1161/01.HYP.0000022606.52221.2F","url":null,"abstract":"Aldosterone breakthrough during ACE inhibitor therapy has been reported. This study investigates changes in plasma aldosterone concentration (PAC) and its mechanism and effects on target organ damage during long-term angiotensin II type 1 (AT1) receptor antagonist (AT1A) therapy in hypertensive rats. An AT1A (candesartan, 1 mg/kg per day PO) was administered in stroke-prone spontaneously hypertensive rats from 4 weeks of age for 34 weeks. PAC was significantly decreased during the first 4 weeks but showed aldosterone breakthrough after 8 weeks of AT1A administration. Plasma angiotensin II concentration was significantly elevated, whereas no change was seen in plasma ACTH or serum potassium. The mechanism(s) of aldosterone breakthrough were investigated by giving high doses of candesartan (3 mg/kg per day PO), dexamethasone (200 &mgr;g/kg per day IP), or the AT2 antagonist (PD123319, 10 mg/kg per day SC) during the last week of the 24-week AT1A treatment period. Dexamethasone and AT2 antagonist but not high-dose AT1A produced a significant decrease in PAC, with a larger decrease produced by the AT2 antagonist. To clarify the effects of the residual aldosterone, effects of coadministration of low-dose spironolactone (10 mg/kg per day SC), an aldosterone antagonist, on left ventricular hypertrophy and expression of brain natriuretic peptide mRNA were determined. Low-dose spironolactone further improved left ventricular hypertrophy and brain natriuretic peptide mRNA expression despite no additional depressor effect. These results suggest that aldosterone breakthrough occurs during long-term AT1A therapy, mainly by an AT2-dependent mechanism. Residual aldosterone may attenuate the cardioprotective effects of AT1A.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"48 1","pages":"28-33"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90364317","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}

引用次数: 129