过氧化物酶体增殖物激活受体双重激动剂WY14643长期给药对血管内皮的保护机制研究

目的通过观察过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptors,PPAR)双重激动剂WY14643对高血压状态下血管内皮收缩因子和环氧化酶信号转导途径的影响,探讨其抗血管收缩及降压保护作用机制。方法选择雄性38~42周的自发性高血压病大鼠(SHR) 40只分为SHR治疗组、SHR对照组各20只,另选取雄性38~42周WKY大鼠20只作为WKY组。SHR治疗组给予WY14643 50 mg/kg灌胃3周,SHR对照组及WKY组给予蒸馏水对照灌胃3周。3周后各组测血压,留取血液样本检测一氧化氮(NO)含量。离取主动脉,在10 ml的组织水浴槽中通过不同药物及试剂干预,探测血管张力的变化。采集浴槽内液体及实验后动脉环采用酶联免疫吸附法及蛋白质免疫印迹法分析血管内皮收缩因子和环氧化酶-1的表达情况。结果与SHR对照组相比,SHR治疗组血压下降,NO含量升高,差异有统计学意义(P 0. 01); SHR治疗组血压和NO水平与WKY组一致(P0. 05)。SHR治疗组血管收缩率较SHR对照组降低(51±5)%(P 0. 05),WKY组无明显血管收缩;在有血管内皮存在的基础上环氧化酶-1表达明显减少(P 0. 05),在无血管内皮存在的基础上环氧化酶-1表达无区别(P0. 05)。SHR治疗组前列腺素F1α、前列腺素F2α和血栓素A_2的释放明显减少(P 0. 05); SHR对照组前列腺素F1α、前列腺素F2α和血栓素A_2的释放情况与WKY组相似(P0. 05)。结论 PPAR双重激动剂WY14643可增加血管舒张因子NO含量,影响环氧化酶的表达,长期给药可能通过减少血管内皮收缩因子起到降压保护作用。     

胰激肽原酶对高血压大鼠心肌MMP-2表达及NO含量的影响

目的本研究通过观察胰激肽原酶对自发性高血压大鼠(SHR)血压及心肌基质金属蛋白酶-2(MMP-2)表达及NO含量的影响,探讨胰激肽原酶的降压及逆转心室重构的作用。方法雄性15周龄SHR 24只,随机分成SHR组、胰激肽原酶小剂量组(7.2 U.kg-1.d-1)、胰激肽原酶大剂量组(14.4 U.kg-1.d-1),每组8只。8只正常WKY大鼠作为阴性对照组。试验4周后结束,测量各组血收缩压(SBP)、左心室重量指数(LVMI)、心肌胶原体积比例(CVF)和心肌血管周围胶原与管腔面积的比例(PVCA)及血清NO含量。心肌组织经VG染色作形态学观察,用免疫组化SP法检测心肌组织切片内MMP-2的表达。结果SHR组SBP、LVMI、CVF、PVCA增高及MMP-2的表达增加,血清NO含量明显下降,较WKY组有显著差异(P<0.05)。应用胰激肽原酶后,给药组NO含量呈剂依赖性的明显升高,接近正常WKY组水平,其余各指标均较SHR组显著下降(P<0.05),但未达到正常WKY组水平。结论胰激肽原酶治疗具有降低SHR血压和逆转心室重构的作用,其机制可能与增加NO含量、抑制心肌MMP-2表达有关。     

氯沙坦对自发性高血压大鼠血管内皮功能和超微结构的影响

目的 :探讨氯沙坦 (lostartan)对自发性高血压大鼠 (SHR)血压、血管内皮细胞功能、内皮细胞超微结构及淋巴细胞钙 [Ca2 ] i的影响。方法 :SHR共 2 8只 ,分成 3组 ,分别为 3月龄对照组 (SHR1) ,6月龄对照组 (SHR2 )和losartan治疗组 (SHR3 )。治疗组从 3月龄开始予losartan 2 0mg·kg-1·d-1治疗至 6月龄。治疗前后检测鼠尾收缩压、淋巴细胞胞浆游离钙 [Ca2 ] i、ET 1、NO ,并观察大鼠肠系膜动脉内皮细胞超微结构。结果 :losartan对SHR有显著降压作用。治疗前SHR的淋巴细胞钙 [Ca2 ] i、ET 1水平均显著性增加 ,NO水平显著下降 ,随鼠龄增大而加大。肠系膜动脉内皮细胞出现明显肿胀、变形 ,比表面均显著减少。经losartan治疗后 ,在降压的同时 ,淋巴细胞[Ca2 ] i、ET 1显著下降 ,NO显著上升 ,血管内皮细胞超微结构的损害得到明显逆转。结论 :细胞内钙在losartan改善高血压血管内皮功能失调作用中可能起着重要的信使作用     

白藜芦醇对自发性高血压大鼠主动脉重塑的影响及机制探讨

目的观察白藜芦醇对自发性高血压大鼠(SHR)动脉重塑的影响,探讨白藜芦醇是否通过ACE2/Ang(1-7)/Mas轴抗动脉重塑。方法将72只大鼠分为血压正常(WKY)组、SHR组、低剂量白藜芦醇干预SHR(SHLR)组、高剂量白藜芦醇干预SHR(SHHR)组,每组18只;WKY组、SHR组给予1 ml生理盐水灌胃;SHLR组给予白藜芦醇2.5mg/(kg·d)+1 ml生理盐水灌胃;SHHR组给予白藜芦醇5 mg/(kg·d)+1 ml生理盐水灌胃;第8周、12周、16周时处死6只大鼠,取动脉血及主动脉组织,评估动脉结构及动脉纤维化;并测定血浆中转化生长因子β1(TGF-β1)、血管紧张素(Ang1-7)的含量以及动脉组织中血管紧张素转化酶2(ACE2)、Mas受体、TGF-β1 mRNA的表达。结果与WKY组相比,SHR组血压明显升高(P0.05),且SHR组血管壁动脉中膜厚度显著增厚,SHLR组和SHHR组SHR动脉中膜厚度明显降低(P0.05);SHLR组和SHHR组动脉中膜胶原纤维含量明显减少(P0.05);低剂量和高剂量白藜芦醇干预能明显降低SHR大鼠血浆TGF-β1含量(P0.05),却能显著升高血浆Ang1-7含量(P0.05);低剂量和高剂量白藜芦醇干预使ACE2 mRNA表达明显升高(P0.05),Mas受体mRNA的表达与ACE2相似,TGF-β1mRNA表达明显降低(P0.05)。结论白藜芦醇对自发性高血压大鼠具有抗动脉重塑的作用;白藜芦醇通过调节ACE2-Ang1-7-Mas轴发挥抗动脉重塑作用。     

心肌组织和血浆IGF—Ⅰ的相关性

本研究采用放射免疫分析法测定自发性高血压大鼠(SHR)和正常血压的Witar—Kyoto大鼠(WKY)血浆和心肌组织中的IGF—Ⅰ水平,以心脏混重(HW)和心脏混生/体重(HW/BW)来判定心肌肥厚。结果显示:SHR的HW较WKY有显著升高(P<0.05),HW/BW则较WKY有高度显著升高(P<0.01)。两组大鼠心肌组织中IGF—Ⅰ与血浆中的IGE—Ⅰ显示正相关(WKY:r=0.8485,P<0.05;SHR:r=0.9529,P<0.005);试验结果提示不论心脏生理和病理情况下,心脏合成和分泌的IGF—Ⅰ对循环中的IGF—Ⅰ水平均有影响,而在心肌肥厚,心肌组织中的IGF—Ⅰ病理水平增高时,影响更为明显。     

老年高血压患者血管内皮舒张功能与内皮素相关性

目的研究老年高血压患者内皮依赖性血管舒张功能和血浆内皮素(ET)的关系。方法检测51例老年高血压患者和15例正常血压老年患者肱动脉的内皮依赖性及内皮非依赖性血管舒张功能,同时测定血浆ET-1含量。结果ET-1含量随血压分级水平递增;高血压各组内皮依赖性血管舒张功能均较对照组明显减弱(P<0.001);线性回归分析表明,内皮依赖性血管舒张功能与血管内皮受损的ET释放水平呈负相关,多元逐步回归分析显示进入影响血管内皮舒张功能方程的唯一因素为收缩压。结论ET测定与超声检测内皮依赖性血管舒张功能具有较好的相关性,但血浆ET水平不能预测内皮依赖性血管舒张功能的损害。高血压是内皮功能受损的独立危险因素。     

中药合剂胃肠术后1号对小肠切除合并腹腔感染大鼠血浆内皮素及一氧化氮的影响

目的　观察小肠切除合并腹腔感染大鼠血中内皮素 (ET)及一氧化氮 (NO)水平的变化 ,及中药合剂胃肠术后 1号的防治作用。方法　取Wistar大鼠 90只 ,随机分为假手术对照组、小肠切除合并腹腔感染模型组和胃肠术后 1号治疗组 ,每组 3 0只。于术后 2 4h、 48h、 72h分批采集静脉血 ,测定血清ET和NO水平。结果　模型组大鼠血中ET、NO含量与假手术组相比明显升高 (P <0 0 5 ) ;胃肠术后 1号治疗组血中ET、NO含量与模型组相比明显降低 (P <0 0 5 )。结论　①ET、NO参与大鼠小肠切除合并腹腔感染病理机制 ;②中药合剂胃肠术后 1号能够降低小肠切除合并腹腔感染大鼠血中ET、NO水平。     

苯磺酸氨氯地平对高血压病患者纤溶活性和内皮血管活性物质的影响

目的观察苯磺酸氨氯地平治疗原发性高血压病(EH)时对纤溶活性、内皮素(ET)、一氧化氮(NO)、降钙素基因相关肽(CGRP)的影响。方法 48名健康体检者作为正常对照组,68例EH患者用苯磺酸氨氯地平治疗8周,观察用药前后血浆组织型纤溶酶原激活物(t-PA)活性、纤溶酶原激活剂抑制物(PAI)活性及ET、NO、CGRP浓度的变化。结果 EH患者t-PA活性、CGRP和NO浓度明显低于正常对照组(P<0.01),而PAI活性、ET浓度明显高于正常对照组(P<0.01),苯磺酸氨氯地平治疗后,血t-PA活性及NO、CGRP浓度均较治疗前显著升高(P<0.01),血PAI活性、血ET浓度显著下降(P<0.01)。结论 EH患者纤溶活性和内皮功能异常,苯磺酸氨氯地平可改善EH患者纤溶性和内皮功能。     

缬沙坦和螺内酯对高血压大鼠心肌c-Jun氨基末端激酶的影响

目的观察血管紧张素Ⅱ受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯对自发性高血压大鼠(SHR)心肌中活化的丝裂原活化蛋白激酶家族(MAPK)中的c-Jun氨基末端激酶(JNK)的影响。方法将18只雄性SHR随机分为三组,每组6只。其中两组分别用缬沙坦30 mg.kg-1.d-1、螺内酯20mg.kg-1.d-1溶于饮水,灌胃,连续治疗13周;对照组给正常饮水,并与Wistar-Kyoto大鼠(WKY)比较。用Western-blot方法检测大鼠心肌磷酸化JNK的表达。结果SHR对照组心肌磷酸化JNK/actin值高于其余三组(P<0.01),缬沙坦组高于螺内酯组和WKY组(P<0.01),螺内酯组与WKY水平接近。两治疗组的LVW/BW较SHR对照组明显减低(均P<0.01),但较WKY对照组有所升高(P<0.05,P<0.01)。两治疗组胶原容积分数(CVF)低于SHR对照组(均P<0.01),高于WKY组(均P<0.05)。结论缬沙坦和螺内酯均能通过抑制心肌中活化的JNK蛋白表达而抑制SHR的左室肥厚和心肌纤维化。     

不同强度运动调控AMPK-SIRT 3通路对自发性高血压大鼠血管功能的影响

摘要 目的：研究不同强度运动对自发性高血压大鼠(spontaneous hypertensive rats,SHR)主动脉血管功能的影响及其可能的机制。 方法：12只京都Wistar大鼠（Wistar-Kyoto Rats,WKY）为安静对照组(WKY-C,n=12),48只SHR随机分为安静对照组(SHR-S,n=12),低强度运动组(SHR-L,n=12),中强度运动组(SHR-M,n=12)和高强度运动组(SHR-H,n=12)。运动组进行14周,每周5次,每次60mins的跑台运动训练。14周运动训练结束后取出胸主动脉,进行血管反应性实验检测主动脉血管功能,Western Blot检测主动脉蛋白水平表达量。 结果：SHR-S组与WKY-C组比较血管功能受损,内皮型一氧化氮合成酶(eNOS)、磷酸化一氧化氮合成酶(p-eNOS)表达下调,血管组织氧化应激水平升高,AMPK-SIRT 3表达下调。运动训练后,SHR-L组和SHR-M组血管功能与血管组织氧化应激水平相比较SHR-S组有明显改善(P<0.05)。SHR-H组与SHR-S组比较血管功能与血管组织氧化应激水平没有改善,乙酰胆碱依赖的血管舒张功能与内皮型一氧化氮合酶的功能降低。与SHR-S组比较,SHR-L组和SHR-M组AMPK-SIRT 3表达水平明显上调(P<0.05),而SHR-H与SHR-S组比较没有明显改变。 结论：低、中强度运动可以有效减轻SHR的主动脉氧化应激并改善血管功能,而高强度运动不能改善SHR的血管功能,其机制可能与AMPK-SIRT 3通路有关。     

替米沙坦对自发性高血压大鼠颈动脉Ⅰ型、Ⅲ型胶原及转化生长因子β_1表达的影响

目的:研究自发性高血压大鼠(SHR)颈动脉Ⅰ型、Ⅲ型胶原及转化生长因子1β(TGF-1β)的表达,并探讨替米沙坦的干预作用。方法:30只雄性12周龄的SHR大鼠随机分为3组:高血压组(SHR)、替米沙坦低剂量组(T e lL)、替米沙坦高剂量组(T e lH),并设同周龄雄性的W KY大鼠为对照组(W KY,n=10),干预18周。观察各组大鼠收缩压(SBP)、免疫组化评估颈动脉Ⅰ型、Ⅲ型胶原及TGF-1β的表达。结果:(1)2周后T e lH组SBP明显低于SHR组(P<0.01),其降压作用持续至实验结束,而T e lL组SBP与SHR组差异无统计学意义(P>0.05);(2)SHR组颈动脉外膜Ⅰ型胶原的表达明显高于W KY组(P<0.01),T e lH、T e lL组颈动脉外膜Ⅰ型胶原的表达低于SHR组(P<0.05);(3)SHR组颈动脉外膜Ⅲ型胶原的表达明显低于W KY组(P<0.01),T e lH组颈动脉外膜Ⅲ型胶原的表达高于SHR组(P<0.01);(4)SHR组颈动脉中膜TGF-1β的IOD值明显低于W KY组(P<0.01),T e lH、T e lL组颈动脉中膜TGF-1β的IOD值高...     

Combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats

Cardiovascular risk factors are associated with reduction in both the number and function of vascular progenitor cells. We hypothesized that 1) hypertension abrogates postnatal vasculogenesis, and 2) antihypertensive treatment based on the combination of perindopril (angiotensin-converting enzyme inhibitor) and indapamide (diuretic) may counteract hypertension-induced alteration in progenitor cell-related effects. Postischemic neovascularization was significantly lower in untreated spontaneously hypertensive rats (SHRs) compared with Wistar Kyoto (WKY) rats (p < 0.05). Treatment of SHRs with perindopril and the combination of perindopril/indapamide reduced the blood pressure levels and normalized vessel growth in ischemic area. Cotreatment with perindopril and indapamide increased vascular endothelial growth factor and endothelial nitric-oxide synthase protein contents, two key proangiogenic factors. It is interesting to note that 14 days after bone marrow mononuclear cell (BM-MNC) transplantation, revascularization was significantly lower in ischemic SHRs receiving BM-MNCs isolated from SHRs compared with those receiving BM-MNCs isolated from WKY rats (p < 0.05). Alteration in proangiogenic potential of SHR BM-MNCs was probably related to the reduction in their ability to differentiate into endothelial progenitor cells in vitro. Furthermore, the number of circulating endothelial progenitor cells (EPCs) was reduced by 3.1-fold in SHRs compared with WKY rats (p < 0.001). Treatments with perindopril or perindopril/indapamide restored the ability of BM-MNCs to differentiate in vitro into EPCs, increased the number of circulating EPCs, and re-established BM-MNC proangiogenic effects. Therefore, hypertension is associated with a decrease in the number of circulating progenitor cells and in the BM-MNC proangiogenic potential, probably leading to vascular complications in this setting. The combination of perindopril and indapamide counteracts hypertension-induced alterations in progenitor cell-related effects and restores blood vessel growth.     

Hypercholesterolemia does not alter endothelial function in spontaneously hypertensive rats

In humans, hypercholesterolemia and hypertension are associated with endothelial dysfunction. Here, we assess whether hypercholesterolemia induces endothelial dysfunction in rats with pre-existing hypertension. Spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were fed with a high-cholesterol diet for 12 weeks, and endothelial function was assessed in isolated thoracic aortic rings. In SHR and WKY rats, the hypercholesterolemic diet resulted in the elevation of total cholesterol and low-density lipoprotein levels by approximately 2.5- and 4.5-fold, respectively. However, in aorta, the basal nitric oxide (NO) production--as assessed by the magnitude of L-NG-nitroarginine methyl ester-induced vasoconstriction as well as the NO-dependent relaxation induced by acetylcholine or histamine--were not diminished either in SHR or in WKY rats fed with the hypercholesterolemic diet. Interestingly, prostacyclin (PGI2) production in aortic rings from SHR rats was higher than in the aorta from WKY rats. However, the hypercholesterolemic diet had no further effects on PGI2 production in the aorta either of SHR or WKY rats. The monocyte chemoattractant protein 1 level in plasma was slightly elevated in SHR and WKY rats fed with the hypercholesterolemic diet compared with their normocholesterolemic counterparts. In summary, even in the presence of pre-existing hypertension, hypercholesterolemia fails to modify NO-dependent and PGI2-dependent endothelial function in SHR rats; it also does not induce a robust inflammatory response. Both are prerequisites for the development of atherosclerosis.     

Radiotelemetric evaluation of hemodynamic effects of long-term ethanol in spontaneously hypertensive and Wistar-Kyoto rats

This study determined the hemodynamic effects of chronic ethanol in telemetered freely moving age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Changes in blood pressure (BP), heart rate (HR), and plasma norepinephrine (as index of sympathetic activity) were evaluated in pair-fed rats receiving liquid diet with or without ethanol (5%, w/v) for 12 weeks. The SHRs exhibited higher baseline BP and lower HR compared with WKY rats. When normalized for body weight, daily ethanol intake was higher in SHRs compared with WKY rats. However, blood ethanol concentration was similar except for a higher level in SHRs at weeks 7 through 9. Ethanol had no effect on BP in WKY rats but caused decreases in BP in SHRs that reached a maximum (approximately 30 mm Hg) at week 5 and remained thereafter. Ethanol also caused reductions in the BP variability and the circadian fluctuations in BP in SHRs but not in WKY rats. Plasma norepinephrine levels were elevated by ethanol in WKY rats, but not in SHRs. The HR was not affected by ethanol in SHRs and showed increases in WKY rats. These findings suggest that chronic ethanol feeding differentially affects BP in SHRs (hypotension) and WKY rats (no effect). The lack of a hypotensive response to ethanol in WKY rats may relate, at least partly, to the associated sympathoexcitation. The present study used the telemetry technique for BP measurement, which eliminates the confounding and stressful effects of other conventional techniques.     

Angiotensin II-induced renal vasoconstriction in genetic hypertension.

Previous studies demonstrate that renovascular responses to angiotensin II (Ang II) are enhanced in spontaneously hypertensive rats (SHRs); however, it is possible that this hyperresponsiveness is mediated by Ang II-induced release of substances from the adrenal gland. Previous studies also show that pertussis toxin normalizes renovascular responses to Ang II in SHRs; however, it is possible that this response is mediated by effects of pertussis toxin on endogenous Ang II levels and/or the sympathoadrenal axis. The purpose of this study was 2-fold: 1) to determine whether the renovascular response to Ang II in SHRs is enhanced even in adrenalectomized SHRs and 2) to determine whether pertussis toxin normalizes enhanced renovascular responses to Ang II when pertussis toxin-induced changes in the renin-angiotensin system and the sympathoadrenal axis are prevented. SHRs and Wistar Kyoto (WKY) rats were anesthetized and administered 20 ml/kg 0.9% saline, and an infusion of aldosterone and hydrocortisone was initiated. After bilateral adrenalectomy, left renal denervation, and pretreatment with captopril, animals received an intrarenal artery infusion of Ang II at 10 ng/kg/min for 5 min. Ang II-induced changes in renal vascular resistance were greater in SHRs compared with WKY rats (p =. 010, n = 19/group). Pertussis toxin (10 microgram/kg i.v. 3 days before the experiment) attenuated Ang II-induced changes in renal vascular resistance in SHR (p <.05), but not in WKY rats (strain x treatment interaction: p =.046). These results suggest that the enhanced renovascular response to Ang II in SHRs is mediated by a G(i)-dependent pathway within the renal vasculature.     

Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats

Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D₁₀₀) were determined and vessels were set up to a normalized internal diameter (0.9 D₁₀₀). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells.     

The Effect of Hypertension on Uncontrolled Hemorrhage in a Rodent Model

Patients with essential hypertension (EH) have higher mortality rates from hemorrhage. How the complex physiologic changes seen in EH affect the response to uncontrolled hemorrhage has yet to be adequately described. OBJECTIVE: To test the null hypothesis that there would be no difference in the hemorrhage volumes and hemodynamic responses to uncontrolled hemorrhage between hypertensive rats (SHRs) and normotensive rats (WKYs). METHODS: Twenty-four adult rats (12 WKYs and 12 SHRs) were anesthetized with althesin via the intra-peritoneal route. The femoral artery was cannulated by cutdown for mean arterial pressure (MAP) measurement and blood gas sampling. Twelve rats (6 WKYs and 6 SHRs) underwent uncontrolled hemorrhage by 50% tail amputation. Twelve rats (6 WKYs and 6 SHRs) served as non-hemorrhage controls. The MAP, base excess (BE), and cumulative blood loss were measured pre-hemorrhage and then every 15 minutes post-hemorrhage for 90 minutes. Data were reported as mean +/- standard error of the mean. Comparisons between control and uncontrolled hemorrhage groups were analyzed by analysis of variance (ANOVA) with repeated-measures post-hoc testing by Bonferroni. Statistical significance was defined by an alpha = 0.05. RESULTS: Mortality rates were significantly higher (p < 0.05) for the SHRs (100%) as compared with the WKYs (33%). Changes in time-averaged MAP post-hemorrhage were significantly greater (p < 0.001) in the SHR group (88 +/- 10 mm Hg) as compared with the WKY group (48 +/- 4 mm Hg). Hemorrhage volume was significantly lower (p = 0.02) in the SHR group (3.7 +/- 0.5 mL) as compared with the WKY group (6.1 +/- 0.7 mL). CONCLUSIONS: Hypertensive rats had a higher mortality rate than normotensives from a comparable vascular injury with lower hemorrhage volumes.     

高血压大鼠肾脏ACE2的表达及其与内皮素的关系

目的探讨自发性高血压大鼠的肾脏中ACE2的表达情况并对其与血浆中内皮素水平做相关分析。方法实验分为对照组和自发高血压组,采用反转录．聚合酶链式反应（RT—PCR）法测定肾脏中ACE2mRNA表达水平,放射免疫法同批检测大鼠血浆中内皮素的含量。结果自发性高血压大鼠和正常对照大鼠相比,肾脏组织中ACE2蛋白的表达下降（P〈0．05）,血清中内皮素的水平升高（P〈0．05）,与ACE2蛋白的表达呈负相关（r=-0．632,P〈0．05）,与血压水平呈正相关（r=0．615,P〈0．05）。结论ACE2在肾脏的表达不同可能是引发高血压病发病的一个重要因素,且其影响血压的机制可能与缩血管物质有关。     

Protective effects of the angiotensin II type 1 (AT1) receptor blockade in low-renin deoxycorticosterone acetate (DOCA)-treated spontaneously hypertensive rats

The present study evaluates the participation of oxidative stress, tissue angiotensin II (Ang II) and endothelin (ET) in the effects of losartan on blood pressure (BP), ventricular hypertrophy and renal injury in spontaneously hypertensive rats (SHRs), and explores how these effects are modified when spontaneous hypertension is transformed in a low-renin model by the administration of deoxycorticosterone acetate (DOCA). The following groups were used: SHR-control, SHR+DOCA, SHR+losartan and SHR+DOCA+losartan. Tail systolic BP was measured once a week. After 9 weeks of treatment, direct BP and metabolic, morphological, biochemical and renal variables were measured. DOCA administration to SHRs produced an increase in BP, ventricular hypertrophy, renal weight, proteinuria, renal histopathological lesions, urinary excretion of isoprostane F2alpha and ET levels in the renal cortex. Losartan reduced BP, plasma malondialdehyde levels, urinary excretion of isoprostane F2alpha, renal Ang II and renal and urinary levels of ET in the SHR and DOCA-treated SHR groups. Losartan increased plasma nitrite/nitrate in SHRs, but not in low-renin DOCA-treated SHRs. Losartan reduced ventricular hypertrophy and ventricular Ang II in SHRs, but not in DOCA-treated SHRs. Losartan significantly decreased proteinuria and renal injury in DOCA-treated SHRs. We conclude that (i) the DOCA-induced aggravation of hypertension, ventricular hypertrophy and renal injury in SHRs is accompanied by augmented oxidative stress and increased levels of ET in the renal cortex, which could contribute to their development; and (ii) losartan reduced oxidative stress and renal Ang II and ET in SHRs and DOCA-treated SHRs, which might contribute to its antihypertensive and renoprotective effects, regardless of renin status.     

Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension

Blood vessel responses to relaxant drugs have been reported to change with aging and with the development of hypertension. In view of the requirement of endothelial cells for the activity of many relaxant drugs, we examined the role of the endothelium in the relaxation response of vascular tissue. Aortic and mesenteric ring segments from normotensive and hypertensive rats, ages 5 to 6, 15 to 18 and 30 to 31 weeks, were examined for relaxation to sodium nitroprusside, sodium nitrite, atrial natriuretic factor and 8-bromo-cyclic GMP. Relaxation responses to the nitrovasodilators were reduced progressively with aging in ring segments of Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) with intact endothelium; however, intact SHR ring preparations displayed less relaxation to nitrovasodilators at 15 to 18 and 30 to 31 weeks than those of WKYs. Rubbed (endothelium denuded) ring preparations displayed greatest relaxation to nitrovasodilators with no difference being observed between SHR and WKY preparations at any age tested. Relaxation to atrial natriuretic factor and 8-bromo-cyclic GMP was not different between rubbed and unrubbed ring segments or between SHRs and WKYs, indicating no detectable impairment of the overall relaxation response in the vascular smooth muscle of SHRs. These results suggest that the total functional capacity of vascular smooth muscle to relax to nitrovasodilators is not changed with aging or hypertension. However, the endothelial cells exert modulatory influences upon the vascular smooth muscle to reduce overall responsiveness to nitrovasodilators, an effect that is enhanced with aging and the development of genetic hypertension.