血府逐瘀汤、天麻钩藤饮、温胆汤对自发性高血压大鼠心肌组织 MAPK 信号通路的影响

目的：观察血府逐瘀汤、天麻钩藤饮、温胆汤对自发性高血压大鼠心肌组织丝裂原活化蛋白激酶信号通路的影响。方法将60只16周龄自发性高血压大鼠随机分为阳性对照组、蛋白酶体抑制剂（ MG-132）组、血府逐瘀汤组、温胆汤组、天麻钩藤饮组各12只,另取12只正常血压大鼠作为阴性对照组。 MG-132组腹腔注射MG-132,血府逐瘀汤组、天麻钩藤饮组、温胆汤组分别给予相应的药物灌胃,阳性对照组、阴性对照组给予等量生理盐水灌胃。连续用药8周后断头处死,取大鼠心脏,采用LiquiChip液相蛋白芯片系统检测各组大鼠心肌组织c-Jun氨基末端激酶（JNK）、p38丝裂原活化蛋白激酶（p38MAPK）、细胞外信号调节激酶5（ERK5）。结果与阴性对照组比较,阳性对照组JNK水平升高,阳性对照组、天麻钩藤饮组、温胆汤组、血府逐瘀汤组、MG132组p38MAPK及ERK5水平升高（P均＜0．01）;与阳性对照组比较,天麻钩藤饮组、温胆汤组、血府逐瘀汤组、MG132组p38MAPK及ERK5水平降低（P均＜0．01）;与MG132组比较,天麻钩藤饮组、温胆汤组、血府逐瘀汤组p38MAPK水平升高（P均＜0．01）;与天麻钩藤饮组、温胆汤组比较,血府逐瘀汤组p38MAPK及ERK5水平降低（P均＜0．05）。结论血府逐瘀汤、天麻钩藤饮、温胆汤可抑制大鼠心肌组织JNK、p38 MAPK、ERK5的表达,血府逐瘀汤较另外两种方剂抑制作用更为明显。     

血府逐瘀汤、温胆汤、天麻钩藤饮对SHR大鼠心肌组织TNF-α、IFN-γ、G-CSF、MCP-1表达的影响

目的观察血府逐瘀汤、温胆汤、天麻钩藤饮对自发性高血压(SHR)大鼠心肌组织中TNF-α、IFN-γ、粒细胞集落刺激因子(G-CSF)、单核细胞趋化蛋白-1(MCP-1)等炎性细胞因子表达的影响。方法将50只16周龄SHR大鼠随机分为5组,SHR对照组、卡托普利组、天麻钩藤饮组、温胆汤组和血府逐瘀汤组各10只;另取10只血压正常的WKY大鼠作为正常对照组。卡托普利组、天麻钩藤饮组、温胆汤组和血府逐瘀汤组分别给予相应的药物灌胃,SHR对照组、正常对照组给予等量生理盐水灌胃,均2次/d,连续灌胃8周。之后断头处死各组大鼠,取其心脏,采用LiquiChip液相蛋白芯片系统检测大鼠心肌组织TNF-α、IFN-γ、G-CSF、MCP-1等炎性细胞因子。结果用药8周后,天麻钩藤饮组、血府逐瘀汤组、温胆汤组大鼠心肌组织TNF-α、G-CSF、MCP-1等炎性细胞因子的表达水平明显降低,IFN-γ的表达升高,与SHR对照组、正常对照组大鼠用药后相比,P均<0.01;血府逐瘀汤组与天麻钩藤饮和温胆汤组相比,P均<0.05。结论血府逐瘀汤、温胆汤、天麻钩藤饮有一定的抗心肌纤维化作用,其机制可能与抑制大鼠心肌组织中TNF-α、G-CSF、MCP-1的表达和提高IFN-γ的表达有关。     

自发性高血压大鼠心肌胶原增生与心肌局部血管紧张素Ⅱ及醛固酮

为探讨高血压大鼠（ＳＨＲ）心肌胶原增生与心肌局部血管紧张素Ⅱ（ＡｎｇⅡ）、醛固酮（Ａｌｄ）的关系。方法应用羟脯氨酸法测定大鼠心肌胶原含量，用放免法测定心肌局部ＡｎｇⅡ、Ａｌｄ含量，将两者进行线性相关分析。结果自发性高血压大鼠（ＳＨＲｎ＝７）与对照组（ＷＫＹｎ＝７）相比，心肌胶原含量增加（Ｐ＜０．０１）。相关分析表明，心肌胶原含量与心肌局部ＡｎｇⅡ含量呈正相关（ｒ＝０．７２，Ｐ＜０．０５），与心肌局部Ａｌｄ含量呈显著正相关（ｒ＝０．８８５，Ｐ＜０．００１），而与血压（ＳＢＰ）无明显相关（ｒ＝０．３９８，Ｐ＞０．０５）。结论ＳＨＲ心肌胶原含量较正常大鼠增加，并且与心肌局部ＡｎｇⅡ、Ａｌｄ含量增加有关。     

天麻钩藤饮对自发性高血压大鼠外周血VEGF、TNF-α及EPCs动员的影响

目的探讨天麻钩藤饮对自发性高血压大鼠血压和血管内皮损伤修复的影响。方法将50只自发性高血压大鼠分为模型组、西药组[依那普利3mg/(kg·d)]、中药低剂量组[1.0mL/(100g·d)]、中剂量组[1.5mL/(100g·d)]和高剂量组[2.0mL/(100g·d)],另设对照组。各组大鼠均灌胃6周,每周测量血压,末次给药后检测外周血内皮细胞生长因子(VEGF)、肿瘤坏死因子α(TNF-α)含量,并对外周血内皮祖细胞进行流式细胞计数。结果与模型组比较,中药高剂量组及西药组大鼠血压降低(P<0.05);中药低剂量组、中剂量组、高剂量组及西药组血清VEGF、TNF-α浓度较模型组均降低,差异均有统计学意义(P<0.01);中药高剂量组及西药组外周血内皮祖细胞数量升高(P<0.05)。结论天麻钩藤饮可降低自发性高血压大鼠血压,其作用机制可能与降低血管内皮细胞损伤、促进内皮祖细胞动员有关。     

自发性高血压大鼠血管合成AngⅡ醛固酮及醛固酮合成酶mRNA表达

目的探讨血管合成血管紧张素Ⅱ及血管合成醛固酮在高血压大鼠中的变化。方法用肠系膜动脉离体灌注，在灌注液中测定血管紧张素Ⅱ及醛固酮。用ＲＴ－ＰＣＲ及Ｓｏｕｔｈｅｒｎｂｌｏｔ法检测醛固酮合成酶基因表达的情况。结果ＳＨＲ血管合成的血管紧张素Ⅱ及醛固酮增多、主动脉组织内醛固酮合成酶基因ｍＲＮＡ表达增强。结论ＳＨＲ血管合成的血管紧张素Ⅱ及醛固酮增多，血醛固酮合成酶基因表达上调。     

牛磺酸对自发性高血压大鼠血压和心肌、血管组织促增殖因子的影响

观察牛磺酸对自发性高血压大鼠（SHR）血压、心肌和主动脉组织促增殖因子（ATⅡ，ET，NE，DA）的影响。结果表明，SHR心肌、主动脉组织AT　Ⅱ，ET含量显著增加，而DA，NE含量则呈消耗性减少。口服牛磺酸能纠正SHR心肌组织牛磺酸的缺乏，降低心肌、主动脉ATⅡ，ET含量，增加DA，NE含量，同时显著降低大鼠血压。提示牛磺酸的降压作用机制可能与抑制心肌血管组织促增殖因子的生成及释放有关。     

依那普利对自发性高血压大鼠心脏局部血管紧张素Ⅱ浓度和左心室结构的影响

目的观察自发性高血压大鼠(SHR)心脏局部血管紧张素Ⅱ(AngⅡ)浓度、左心室结构以及依那普利对其影响.方法12周龄SHR 40只,随机分为依那普利[30 mg/(kg·d)]治疗组(SHR-d组)和对照组(SHR组)两组,另设同周龄的正常血压大鼠20只(WKY组)作为对照,共观察12周.第1周和第12周测血压和体重,处死后分别测量左心室重量、左心室室壁厚度,放免法检定心肌AngⅡ浓度,应用病理学图像分析法对各组大鼠左室心肌细胞的长、短径、截面积和心肌胶原体积比例(CVF)、心肌血管周围胶原面积和管腔面积比例(PVCA)进行测量.结果1)SHR-d组血压、AngⅡ浓度显著低于SHR组而接近WKY组(P＜0.05).2)SHR-d组CVF(1.98%±1.57%vs 5.11%±2.25%)、PVCA(0.68%±0.19%vs 1.20%±0.19%)、LV/BW比值(3.14±0.31 vs4.09±0.21)mg/g,左心室室壁厚度(0.32±0.05 vs 0.43±0.03)cm均明显低于SHR组(P＜0.05).3)SHR-d组的心肌细胞长、短径和截面积数值均较SHR组下降,但未降到正常.结论应用依那普利能有效抑制SHR心脏局部AngⅡ生成,能部分逆转SHR的左室肥厚.     

依那普利对自发性高血压大鼠心脏局部血管紧张素Ⅱ浓度和左心室结构的影响

目的观察自发性高血压大鼠(SHR)心脏局部血管紧张素Ⅱ(AngⅡ)浓度、左心室结构以及依那普利对其影响。方法12周龄SHR40只,随机分为依那普利[30mg/(kg·d)]治疗组(SHRd组)和对照组(SHR组)两组,另设同周龄的正常血压大鼠20只(WKY组)作为对照,共观察12周。第1周和第12周测血压和体重,处死后分别测量左心室重量、左心室室壁厚度,放免法检定心肌AngⅡ浓度,应用病理学图像分析法对各组大鼠左室心肌细胞的长、短径、截面积和心肌胶原体积比例(CVF)、心肌血管周围胶原面积和管腔面积比例(PVCA)进行测量。结果1)SHRd组血压、AngⅡ浓度显著低于SHR组而接近WKY组(P<0.05)。2)SHRd组CVF(1.98%±1.57%vs5.11%±2.25%)、PVCA(0.68%±0.19%vs1.20%±0.19%)、LV/BW比值(3.14±0.31vs4.09±0.21)mg/g,左心室室壁厚度(0.32±0.05vs0.43±0.03)cm均明显低于SHR组(P<0.05)。3)SHRd组的心肌细胞长、短径和截面积数值均较SHR组下降,但未降到正常。结论应用依那普利能有效抑制SHR心脏局部AngⅡ生成,能部分逆转SHR的左室肥厚。     

天麻钩藤饮联合硝苯地平治疗高血压患者的疗效及其对血清Res、APN水平的影响

目的:研究天麻钩藤饮治疗高血压患者的疗效及对血清抵抗素(Res)、脂联素(APN)水平的影响.方法:我院的240例高血压患者被随机均分为硝苯地平组与联合治疗组(在硝苯地平组基础上加用天麻钩藤饮),两组均治疗8周.观察比较两组治疗前后收缩压、舒张压、血清Res、APN水平以及治疗总有效率.结果:联合治疗组总有效率显著高于...     

血管紧张素Ⅱ1型受体拮抗剂与醛固酮受体拮抗剂对逆转高血压大鼠心肌重塑的作用

在受体水平阻断肾素—血管紧张素系统 ,比较血管紧张素Ⅱ 1型受体拮抗剂与醛固酮受体拮抗剂对逆转高血压心肌重塑的作用 ,来探讨高血压性心肌重塑的可能机理。为此 ,制作二肾一夹型高血压大鼠模型形成心肌肥厚及纤维化 ,然后分成高血压对照组、缬沙坦组 [10 μg (kg·d) ]和螺内酯组 [4 0mg (kg·d) ]。分别观察给药前、给药后 4周和 12周血浆及心肌血管紧张素Ⅱ和醛固酮含量、左心室重量指数、心肌胶原含量、心肌胶原容积分数及Ⅰ、Ⅲ型胶原的病理特征。结果发现 ,与高血压对照组比较 ,缬沙坦组左心室重量指数、心肌胶原含量和心肌胶原容积分数显著下降 (P <0 .0 5 ) ,以降低Ⅰ型胶原沉积为主 ;螺内酯组左心室重量指数、心肌胶原含量和心肌胶原容积分数亦有所下降 (P <0 .0 5 ) ,以降低Ⅲ型胶原沉积为主 ,但作用不如缬沙坦。结果提示 ,左心室肥厚发展过程与心肌纤维化存在异时性。血管紧张素Ⅱ和醛固酮在心肌重塑过程中起关键作用 ,血管紧张素Ⅱ 1型受体可能主要介导Ⅰ型胶原的沉积 ,而醛固酮受体可能主要介导Ⅲ型胶原的沉积。     

Effect of long-term ACE inhibition on myocardial tissue in hypertensive stroke-prone rats.

The aim of the study was to investigate the influence of long-term ACE inhibition with ramipril on myocardial hypertrophy and its molecular background in spontaneously hypertensive stroke-prone rats (SHR-SP). Therefore, 1-month-old pre-hypertensive SHR-SP were randomized into three groups and exposed lifelong via drinking water to 1 mg/kg/day ramipril (anti-hypertensive dose, RHI), 10 micrograms/kg/day ramipril (non-anti-hypertensive dose, RLO) or placebo. After 15 months cardiac tissue was collected from ten rats each for immunohistochemistry and Northern blot analysis of structural proteins, proteins of the extracellular matrix and several growth factors. Results showed that RHI, but not RLO, treatment prevented development of myocyte hypertrophy (ANP). Furthermore, unlike placebo-treated rats, the ramipril-treated animals had no evidence of degeneration and loss of structural proteins (alpha -actinin), inflammatory infiltrates (CD45) and deposition of extracellular matrix proteins (collagen, fibronectin, vimentin). Only in RHI-treated animals, mRNA levels for TGF- beta(1)as well as of collagen alpha(1)(I) and fibronectin were downregulated compared to placebo-treated animals. In contrast, VEGF mRNA levels increased significantly in both groups of ramipril-treated animals v. placebo-treated SHR-SP. Thus, the reported life prolonging effect of high doses of ramipril which is associated with prevention of hypertension and hypertrophy is accompanied by prevention of the development of necrosis and fibrosis. The role of VEGF, however, seems to be independent of this effect.     

吡格列酮对老年自发性高血压大鼠心肌纤维化及胶原代谢的影响

目的探讨吡格列酮对老年自发性高血压大鼠(SHRs)心肌纤维化及胶原代谢的影响和可能机制。方法 12月龄SHRs分为吡格列酮组和SHR组,同月龄WKY鼠为对照组。观察大鼠体重及尾动脉血压、测定左室重量指数(LVI)、心肌胶原定性分析、测定心肌羟脯氨酸含量、Westen印迹法检测心肌基质金属蛋白酶(MMP)-1、MMP抑制物(TIMP)-1蛋白表达、测定心肌活性氧(ROS)和超氧化物歧化酶(SOD)水平并观察心肌过氧化物酶体增殖物激活受体(PPAR)γmRNA表达和组织定位。结果与对照组相比,SHR组血压、胶原容积积分、血管周围胶原面积和左室心肌组织羟脯氨酸浓度明显升高,吡格列酮组能改善心肌纤维化;SHR组MMP-1/TIMP-1显著降低,吡格列酮组MMP-1/TIMP-1水平显著升高,PPARγ表达增多,心肌ROS浓度显著下降(P0.05)。结论吡格列酮通过调节MMPs/TIMP平衡促进胶原降解,抑制胶原的沉积,抑制心肌纤维化,机制可能是通过激活PPARγ和抑制ROS的形成。     

黄芪对自发性高血压大鼠早期肾组织NO和NOS的影响

目的研究黄芪对自发性高血压大鼠（SHR）早期肾功能保护作用及其机制,并比较黄芪与依那普利对高血压早期肾损害的延缓作用及对肾脏内皮功能保护作用的疗效。方法将24只l2周龄SHR大鼠随机分为3组:黄芪组、依那普利组及生理盐水组,同时以8只同龄Wistar-Kyoto（WKY）大鼠作为正常对照组。分别检测尿微量白蛋白,以20200 mg/L为早期肾损害标准,黄芪组及依那普利组分别以黄芪和依那普利灌胃8周,其余灌胃等量生理盐水。结果与WKY大鼠比较,SHR的血压显著升高（P<0.05）;尿微量白蛋白（MA）和β2-微球蛋白（β2-MG）显著升高（P<0.05）;肾组织一氧化氮（NO）含量及一氧化氮合酶（NOS）活性显著降低（P<0.05）。黄芪和依那普利干预后,与生理盐水组比较,尿MA和β2-MG显著下降,肾组织NO及NOS显著升高（P<0.05）,两者组间比较无显著差异。结论黄芪能明显降低SHR尿MA和β2-MG水平,延缓高血压早期肾损害,其机制与增加肾组织NO含量及NOS活性以改善高血压早期肾脏内皮功能有关。其作用与依那普利相当。     

上调血红素氧合酶1对高血压合并心肌梗死后心力衰竭的作用

目的研究上调血红素氧合酶1(HO-1)对高血压合并心肌梗死大鼠模型血压及心功能的影响。方法选择同为13周龄的雄性自发性高血压大鼠40只及雄性Wistar大鼠20只,随机分为6组,假手术组、对照组、高血压组、模型组、诱导剂组(钴原卟啉4.5mg/kg)、抑制剂组(锡中卟啉15mg/kg),每组10只。术后第1天开始给药,腹腔注射,1次/周,持续6周后,进行相关指标的检测。结果与模型组比较,诱导剂组的血压显著降低,心肌梗死面积缩小,LVEF、左心室短轴缩短率、左心室压力最大上升和下降速率/左心室收缩压峰值升高;左心室舒张末内径、左心室收缩末内径和全心重/体质量下降;血清C反应蛋白、白细胞介素6水平降低,血清总胆红素、一氧化氮、前列环素水平升高(P<0.05,P<0.01)。与诱导剂组比较,抑制剂组血压与心功能的改善情况被阻断。结论上调HO-1能通过抑制炎性反应、抑制左心室重构、改善内皮功能紊乱等机制,降低高血压合并心肌梗死大鼠模型的血压,提高梗死后心功能。     

Effect of capsaicin on plasma and tissue levels of insulin-like growth factor-I in spontaneously hypertensive rats.

OBJECTIVE: Plasma levels of insulin-like growth factor-I (IGF-I), an important substance for maintaining cardiovascular homeostasis, are lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar Kyoto rats (WKY). Calcitonin gene-related peptide (CGRP) increases IGF-I production in vitro and in vivo, suggesting that stimulation of sensory neurons might increase the production of IGF-I in SHR. DESIGN: Levels of CGRP and IGF-I in plasma, kidneys and heart in WKY and SHR and cellular cyclic AMP levels in dorsal root ganglion neurons (DRGs) isolated from WKY and SHR were measured by an ELISA-based method. RESULTS: Levels of CGRP and IGF-I in plasma, kidneys and heart of SHR were about half of those of WKY. Administration of capsaicin significantly increased levels of CGRP and IGF-I in plasma and tissues of SHR to the levels in WKY and these increases were completely reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation. CGRP release and cellular levels of cAMP in DRGs isolated from SHR were significantly lower than those in DRGs isolated from WKY. Capsaicin increased both CGRP release and cellular cAMP levels in DRGs isolated from SHR to the levels in DRGs isolated from WKY. CONCLUSIONS: Sensory neuron activation might be lower in SHR than in WKY probably due to decreased production of cAMP in sensory neurons, explaining why IGF-I levels in plasma and tissues are lower in SHR than in WKY.     

Higher level of plasma nitric oxide in spontaneously hypertensive rats.

We had detected a slightly, but significantly, higher level of plasma nitrite/nitrate in the spontaneously hypertensive rat (SHR) by using the nitric oxide (NO) analyzer (Sievers 280 NOA), which converts nitrate (including nitrate converted from nitrite) to NO. Here, we examined whether the release of NO from protein-bound dinitrosyl nonheme iron complexes (DNIC) contributes to the elevated plasma nitrate level in the SHR. The SHR and their genetic normotensive controls, Wistar-Kyoto rats (WKY), were anesthestized and cannulized for monitoring blood pressure, collecting a blood sample, and the administration of endotoxin (lipopolysaccharide [LPS]). The nitrate levels (an indicator of NO formation) in the plasma and the aorta were measured by an NO analyzer. In addition, the relaxation of acetylcholine (ACh) in the presence or absence of N(omega)-nitro-L-arginine methyl ester (L-NAME) was also examined in thoracic aortae obtained from both strains. The slight, but significant, increase of basal nitrate levels in the plasma and aorta were observed, and the former was further enhanced in SHR treated with LPS for 3 h. In vitro, the ACh-induced relaxation was attenuated in the aortae obtained from SHR. However, this difference between SHR and WKY (without LPS treatment) was abolished by treatment of rings with L-NAME (30 micromol/L), suggesting that an impairment of NO formation was observed in the SHR. After rats were treated with LPS for 3 h, the ACh-induced relaxation was reduced in the WKY, but not in the SHR. In addition, a 10-fold increase of L-NAME was needed to abolish the difference in ACh-induced relaxation between SHR and WKY, indicating an expression of inducible NO synthase in both strains treated with LPS. We suggest that the elevated plasma NO level in SHR may be due to the release of NO from DNIC in the vascular bed to combat the hypertensive state.     

坎地沙坦对自发性高血压大鼠骨骼肌胰岛素敏感性的影响

目的探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARB)坎地沙坦对自发性高血压大鼠(SHR)骨骼肌胰岛素敏感性的影响及其机制。方法 30只SHR随机分为模型组、坎地沙坦高剂量组(Can 1组)及坎地沙坦低剂量组(Can 2组),每组10只,另选10只WKY大鼠作为对照组。均给予果糖喂养,Can 1组(0.8 mg/kg)、Can 2组(0.4mg/kg)分别给予坎地沙坦灌胃干预,观察第8周末各组大鼠胰岛素抵抗指数(HOMA-IR)和AngⅡ的水平,以及骨骼肌蛋白激酶B(Akt)的基因及蛋白表达水平。结果与对照组比较,模型组大鼠AngⅡ、HOMA-IR及血清空腹胰岛素(FINS)明显升高,骨骼肌中Akt mRNA表达及P-Akt蛋白表达显著减少,差异有统计学意义(P<0.05,P<0.01)。与模型组比较,Can 1组大鼠FINS、HOMA-IR明显降低,Can 1组和Can 2组骨骼肌Akt mRNA表达及P-Akt表达显著增加,差异有统计学意义(P<0.05,P<0.01)。结论 AngⅡ通过下调SHR骨骼肌的Akt蛋白表达引起胰岛素抵抗,而坎地沙坦通过抑制AngⅡ的这种作用改善骨骼肌胰岛素抵抗。     

Effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats

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可溶性细胞间黏附分子-1在自发性高血压大鼠肾损害作用的研究

目的研究可溶性细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)在自发性高血压大鼠(spontaneously hypertensive rat,SHR)肾脏的表达及其与肾损害的关系。方法以同龄雄性正常血压大鼠(WistarKyoto,WKY)和SHR为研究对象,分别于12周龄和24周龄时检测2种大鼠尾动脉血压、肾功能及β2微球蛋白(β2-MG),并采用免疫组织化学的方法检测ICAM-1在肾脏中的表达。结果同WKY组比较,SHR组24周时β2-MG显著增高(P<0.01),而且尾动脉收缩压(SBP)显著性增高;而尿素氮(BUN)和血肌酐(SCr)的差异无显著性(P>0.05)。ICAM-1在WKY组肾小管的表达无或极微量;在SHR组的肾小球有少量表达,但在肾小管的表达显著,且随高血压病程的进展,ICAM-1的表达显著性增加(P<0.01)。结论ICAM-1在SHR肾小管的表达显著增加,与肾损害的各项指标呈正相关。     

Effect of nifedipine and enalapril on insulin-induced glucose disposal in spontaneous hypertensive and diabetic rats

Hypertension and diabetes mellitus are associated with hyperinsulinemia and insulin resistance. The present work was undertaken to study the effects of enalapril and nifedipine on insulin sensitivity in spontaneously hypertensive (SH) rats and diabetic rats. Insulin sensitivity was measured by insulin tolerance test using K(ITT) as an index of insulin mediated glucose metabolism. The time to produce 50% fall in initial blood sugar level (T1/2) was significantly higher in non-insulin dependent diabetes mellitus (NIDDM) and SH rats as compared to Wistar control. The mean K(ITT) values were significantly lower in NIDDM and SH rats as compared to Wistar control. Treatment with nifedipine (10 mg/kg) and enalapril (5 mg/kg) for 15 days produced a significant reduction in T1/2. Further, K(ITT) value was found to be significantly increased in SH rats treated with nifedipine or enalapril as compared to control. Our data indicate that NIDDM and SH rats are not only hyperinsulinemic but also insulin resistant. Nifedipine and enalapril treatment produced increase in insulin sensitivity in these animals.