自发性高血压大鼠肾脏血管紧张素转换酶2 mRNA转录及其蛋白表达

目的观察不同月龄自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2) mRNA转录及其蛋白表达,初步探讨ACE2在高血压发生、发展过程中的可能作用。方法雄性SHR1月龄组(S1)、2月龄组(S2)、3月龄组(S3)、6月龄组(S6)和9月龄组(S9)共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto(WKY)大鼠作对照。采用RBP-Ⅰ型大鼠血压心率测定仪测量大鼠尾动脉收缩压(SBP);逆转录聚合酶链式反应(RT-PCR)法检测肾脏ACE2 mRNA的转录水平;免疫组化染色结合计算机图像分析方法测定肾脏ACE2蛋白的表达水平。结果1)SHR的SBP随着月龄的增加而上升,6月龄后趋于稳定。2)SHR和WKY肾脏ACE2蛋白和 mRNA水平均随着月份的增加而增加,3月龄时达高峰,6月龄后趋于稳定;且SHR肾脏ACE2蛋白和 mRNA水平均低于同龄的WKY。S1肾脏髓质内侧部ACE2免疫染色阳性面积百分比较皮质和髓质外侧部高,与1月后的分布相反。结论1)SHR肾脏ACE2 mRNA和蛋白的表达水平比WKY大鼠低。2)大鼠肾脏ACE2 mRNA和蛋白的表达具有时间和部位分布上的差异。     

自发性高血压大鼠肾脏血管紧张素转换酶2 mRNA转录及其蛋白表达

目的 观察不同月龄自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)mRNA转录及其蛋白表达,初步探讨ACE2在高血压发生、发展过程中的可能作用.方法 雄性SHR 1月龄组(S1)、2月龄组(S2)、3月龄组(S3)、6月龄组(S6)和9月龄组(S9)共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto(WKY)大鼠作对照.采用RBP-Ⅰ型大鼠血压心率测定仪测量大鼠尾动脉收缩压(SBP);逆转录聚合酶链式反应(RT-PCR)法检测肾脏ACE2 mRNA的转录水平;免疫组化染色结合计算机图像分析方法 测定肾脏ACE2蛋白的表达水平.结果 1)SHR的SBP随着月龄的增加而上升,6月龄后趋于稳定.2)SHR和WKY肾脏ACE2蛋白和mRNA水平均随着月份的增加而增加,3月龄时达高峰,6月龄后趋于稳定;且SHR肾脏ACE2蛋白和mRNA水平均低于同龄的WKY.S1肾脏髓质内侧部ACE2免疫染色阳性面积百分比较皮质和髓质外侧部高,与1月后的分布相反.结论 1)SHR肾脏ACE2 mRNA和蛋白的表达水平比WKY大鼠低.2)大鼠肾脏ACE2 mRNA和蛋白的表达具有时间和部位分布上的差异.     

水孔蛋白2(AQP2)在SHR和WKY大鼠肾脏的不同表达

目的本研究旨在探讨SHR和WKY大鼠肾脏中,AQP2 mRNA是否存在差异表达及其和精氨酸加压素(AVP)的关系.方法成年SHR和WKY大鼠各9只,12周龄,体重200～300 g.断头取血,放免法测定血浆AVP含量.取肾脏近髓组织100 mg,RT-PCR法检测大鼠肾脏AQP2mRNA的表达量,数据以-x±s表示.结果 SHR肾脏AQP2mRNA表达水平显著高于WKY(0.801±0.08vs0.571±0.06,P＜0.05),SHR血浆中AVP的浓度显著高于WKY(90±17.83 vs60.82±12.59)pg/mL.结论 SHR肾脏AQP2 mRNA表达量上调,可能在SHR高血压的发生发展中发挥着一定的作用,AVP可能介导了AQP2 mRNA表达.     

自发性高血压大鼠肾上腺髓质素含量与中性内肽酶分布的关系

目的 测定自发性高血压大鼠(SHR)与WKY大鼠组织肾上腺髓质素(ADM)含量和中性内肽酶(NEP)活性及其表达水平，以探讨NEP的变化在高血压时组织ADM水平升高中的意义。方法 采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性，同时用半定量RT-PCR和免疫组织化学染色法分别检测组织NEP mRNA和NEP蛋白的表达和分布。结果 ADM和NEP广泛分布于大鼠的血浆和组织，SHR的ADM含量在各组织普遍高于WKY大鼠。SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠，ADM含量与NEP活性呈负相关。反之，SHR血浆和肾脏NEP活性、肾脏NEP mRNA水平与蛋白量均高于WKY大鼠，ADM含量与NEP活性呈正相关。在肺脏和主动脉，NEP的活性无明显变化。结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致，提示高血压时组织局部的NEP对ADM含量的影响不同。     

水孔蛋白2（AQP2）在SHR和WKY大鼠肾脏的不同表达

目的　本研究旨在探讨SHR和WKY大鼠肾脏中 ,AQP2mRNA是否存在差异表达及其和精氨酸加压素 (AVP)的关系。方法　成年SHR和WKY大鼠各 9只 ,12周龄 ,体重 2 0 0～ 3 0 0g。断头取血 ,放免法测定血浆AVP含量。取肾脏近髓组织 10 0mg ,RT PCR法检测大鼠肾脏AQP2mRNA的表达量 ,数据以 x±s表示。结果　SHR肾脏AQP2mRNA表达水平显著高于WKY( 0 80 1± 0 0 8vs 0 5 71± 0 0 6,P <0 0 5 ) ,SHR血浆中AVP的浓度显著高于WKY( 90± 17 83vs60 82± 12 5 9) pg/mL。结论　SHR肾脏AQP2mRNA表达量上调 ,可能在SHR高血压的发生发展中发挥着一定的作用 ,AVP可能介导了AQP2mRNA表达     

苯那普利、缬沙坦对自发性高血压大鼠肾脏血管紧张素转换酶2表达的影响

目的观察苯那普利与缬沙坦对自发性高血压大鼠(SHR)血浆血管紧张素Ⅱ(Ang Ⅱ)和肾脏血管紧张素转换酶2(ACE2)表达水平的影响,探讨ACE2在高血压发病机制和药物治疗中的意义.方法12周龄雄性SHR 28只,分为空白对照组(Sc)、苯那普利组(10 mg/kg·d)(Sb)、小剂量缬沙坦组(10 mg/kg·d)(Sl)、大剂量缬沙坦组(30 mg/kg·d)(Sh),每组7只,7只雄性WKY大鼠为正常对照.药物治疗3月后,用放射免疫法测定血浆Ang Ⅱ含量,RT-PCR法测定肾脏中ACE和ACE2 mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达.结果与WKY大鼠相比,SHR肾脏中ACE2 mRNA及其蛋白的表达均明显降低,而ACE mRNA的表达和血浆Ang Ⅱ水平则明显升高(P<0.05).缬沙坦治疗后SHR血压显著下降而血浆Ang Ⅱ水平则进一步升高,肾脏中ACE2的表达水平明显升高,且呈剂量依赖性(P<0.05).苯那普利治疗对SHR血浆Ang Ⅱ水平及肾脏ACE2的表达则无明显影响.结论SHR体内ACE和ACE2的表达失衡可能在高血压的发病机制中有重要意义.血管紧张素受体拮抗剂(ARB)可能通过升高SHR血浆Ang Ⅱ的水平而增加肾脏中ACE2的表达,ACE2表达的增加可能是ARB抗高血压治疗的一个新药理机制.     

ACE2和ACE在自发性高血压大鼠心肌中的变化

目的:观察自发性高血压大鼠(SHR)心肌的血管紧张素转化酶(ACE)和ACE2的表达,以探讨ACE2和ACE在高血压发生发展中的变化。方法:取15只SHR,处死,分离左心室,行RT-PCR、Western blot蛋白质免疫印迹和免疫组织化学检测ACE及ACE2表达;同步取10只WKY大鼠作为正常血压对照组。结果:SHR组心肌ACE的mRNA和蛋白质表达都显著高于WKY组[(1.68±0.34)∶(0.33±0.12),P<0.05;(1.21±0.14)∶(0.71±0.11),P<0.05],而ACE2的mRNA和蛋白质表达皆明显低于WKY组[(0.50±0.15)∶(1.16±0.24),P<0.05;(0.71±0.24)∶(1.22±0.14),P<0.05)]。免疫组织化学染色显示,SHR组ACE的阳性率明显高于WKY组(87%∶50%,P<0.05),而ACE2的阳性率明显低于WKY组(27%∶70%,P<0.05)。结论:SHR心肌ACE明显升高,ACE2显著降低;SHR高血压发生发展过程中存在着ACE和ACE2表达的失衡。     

自发性高血压大鼠肾上腺髓质素含量与中性内肽酶分布的关系

目的测定自发性高血压大鼠(SHR) 与WKY大鼠组织肾上腺髓质素(ADM)含量和中性内肽酶(NEP)活性及其表达水平,以探讨NEP的变化在高血压时组织ADM水平升高中的意义.方法采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性,同时用半定量RT-PCR和免疫组织化学染色法分别检测组织NEP mRNA和NEP蛋白的表达和分布.结果 ADM和NEP广泛分布于大鼠的血浆和组织,SHR的ADM含量在各组织普遍高于WKY大鼠.SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠,ADM含量与NEP活性呈负相关.反之,SHR血浆和肾脏NEP活性、肾脏NEP mRNA水平与蛋白量均高于WKY大鼠,ADM含量与NEP活性呈正相关.在肺脏和主动脉,NEP的活性无明显变化.结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致,提示高血压时组织局部的NEP对ADM含量的影响不同.     

苯那普利、缬沙坦对自发性高血压大鼠肾脏血管紧张素转换酶2表达的影响

目的观察苯那普利与缬沙坦对自发性高血压大鼠(SHR)血浆血管紧张素Ⅱ(AngⅡ)和肾脏血管紧张素转换酶2(ACE2)表达水平的影响,探讨ACE2在高血压发病机制和药物治疗中的意义。方法12周龄雄性SHR28只,分为空白对照组(Sc)、苯那普利组(10mg/kg.d)(Sb)、小剂量缬沙坦组(10mg/kg.d)(Sl)、大剂量缬沙坦组(30mg/kg.d)(Sh),每组7只,7只雄性WKY大鼠为正常对照。药物治疗3月后,用放射免疫法测定血浆AngⅡ含量,RT-PCR法测定肾脏中ACE和ACE2mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达。结果与WKY大鼠相比,SHR肾脏中ACE2mRNA及其蛋白的表达均明显降低,而ACEmRNA的表达和血浆AngⅡ水平则明显升高(P<0.05)。缬沙坦治疗后SHR血压显著下降而血浆AngⅡ水平则进一步升高,肾脏中ACE2的表达水平明显升高,且呈剂量依赖性(P<0.05)。苯那普利治疗对SHR血浆AngⅡ水平及肾脏ACE2的表达则无明显影响。结论SHR体内ACE和ACE2的表达失衡可能在高血压的发病机制中有重要意义。血管紧张素受体拮抗剂(ARB)可能通过升高SHR血浆AngⅡ的水平而增加肾脏中ACE2的表达,ACE2表达的增加可能是ARB抗高血压治疗的一个新药理机制。     

缬沙坦对自发性高血压大鼠肾脏的保护作用

目的探讨缬沙坦对自发性高血压大鼠(SHR)肾脏的保护作用,以及与结缔组织生长因子(CTGF)在SHR肾脏中表达的关系。方法本实验以12周龄雄性SHR和同龄雄性WistarKyotoRats(WKY)大鼠为研究对象,SHR分为治疗组[缬沙坦,30mg/(kg·d)、灌胃]与对照组,WKY大鼠为正常对照组,测量不同时期(12周,24周)大鼠尾动脉压、肾功能、尿β2微球蛋白(β2MG)的变化情况,以及用免疫组化的方法观察结缔组织生长因子在肾脏中的表达。结果12周后,相对于同龄WKY大鼠、SHR治疗组而言,SHR对照组的尿素氮、血肌酐变化无显著意义,而尾动脉压、尿β2MG均有显著增高(P<0.01,P<0.05)。经免疫组化半定量检测显示:在24周龄SHR对照组,其肾脏中CTGF的表达相对于同龄WKY大鼠及SHR治疗组明显升高(P<0.01),同时与尿β2MG的水平成正比(P<0.05)。结论缬沙坦能显著减少尿蛋白,同时使CTGF在SHR肾脏的表达明显减少,说明CTGF可能是慢性高血压导致的肾损害的重要机制之一。     

Isolation of preferentially expressed genes in the kidneys of hypertensive rats

By differential hybridization, three complementary DNAs designated as S3, S2, and SA were isolated, and the corresponding messenger RNAs (mRNAs) were differentially expressed between the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. S3 is identical to cytochrome P450 IV A2. SA encoded a protein of 546 amino acid residues, and its carboxyl terminal region had a slight homology to luciferase. No homologous sequence has been reported in S2 sequences. S3 mRNA was about four times more abundantly expressed in the kidneys of 28-day-old SHR than in those of age-matched WKY rats, but there was no difference at age 16 weeks. A low NaCl diet positively modulated the expression of the S3 gene. S2 mRNA was almost undetectable in the kidneys of 28-day-old WKY rats but was clearly detected in those of age-matched SHR. The expression level of S2 mRNA in the livers of 16-week-old SHR was about five times higher than that of age-matched WKY rats. The expression of S2 mRNA in the livers was modulated by dietary NaCl and captopril. SA mRNA was more than 10 times more abundantly expressed in the kidneys of SHR than in those of WKY rats from age 4 weeks. With the administration of captopril, the expressions of SA mRNA in the livers of SHR were positively modulated. Because these three genes are not only differentially expressed between SHR and WKY rats but also related to sodium metabolism or blood pressure control, the identification of these genes may provide important probes to examine the mechanisms of hypertension.     

Urapidil in normotensive and spontaneously hypertensive rats: the effects on systemic and regional haemodynamics and cardiac mass

The effects of treatment for three weeks with urapidil (10 mg/kg p.o. twice daily) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Urapidil decreased mean arterial pressure and total peripheral resistance index (176 +/- 3 versus 145 +/- 5 mmHg and 0.61 +/- 0.02 versus 0.49 +/- 0.02 units, respectively; each P less than 0.01) in SHR without affecting heart rate, cardiac index or cardiac mass. No systemic haemodynamic changes were observed in WKY rats. All organ vascular resistances decreased significantly in SHR and blood flow increased to skin (P less than 0.01) and kidneys (P less than 0.05). These data indicate that urapidil is a potent antihypertensive agent in SHR which reduced mean arterial pressure through a decreased total peripheral resistance that was distributed throughout all circulations. Despite these haemodynamic changes, cardiac mass did not change.     

Differential regulation of cardiac adrenomedullin and natriuretic peptide gene expression by AT1 receptor antagonism and ACE inhibition in normotensive and hypertensive rats

OBJECTIVE: To study the effects of long-term treatment with the type 1 angiotensin (AT1) receptor antagonist losartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril, on cardiac adrenomedullin (ADM), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression. METHODS: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were given losartan (15 mg/kg per day) or enalapril (4 mg/kg per day) orally for 10 weeks. The effects of drugs on systolic blood pressure, cardiac hypertrophy, ANP, BNP and ADM mRNA and immunoreactive-ANP (IR)-ANP, IR-BNP and IR-ADM levels in the left ventricle and atria were compared. RESULTS: Losartan and enalapril treatments completely inhibited the increase of systolic blood pressure occurring with ageing in SHR. The ratio of heart to body weight was reduced in both losartan- and enalapril-treated SHR and WKY rats. Treatment with losartan or enalapril reduced left ventricular ANP mRNA and IR-ANP in both strains, and ventricular BNP mRNA levels in SHR rats. Inhibition of ACE, AT1 receptor antagonism, changes in blood pressure or cardiac mass had no effect on left ventricular ADM gene expression in SHR and WKY rats. In addition, atrial IR-ANP and IR-ADM levels increased in SHR whereas IR-BNP levels decreased in WKY and SHR rats in response to drug treatments. CONCLUSIONS: Our results show that ventricular ADM synthesis is an insensitive marker of changes in haemodynamic load or cardiac hypertrophy. Furthermore, the expression of ADM, ANP and BNP genes is differently regulated both in the left ventricle and atria in response to AT1 receptor antagonism and ACE inhibition.     

Hemodynamic Effects of Prolonged Treatment with Diltiazem in Conscious Normotensive and Spontaneously Hypertensive Rats

To determine systemic and regional hemodynamic effects of prolonged treatment with the calcium antagonist diltiazem (30 mg/kg twice daily by gastric gavage, for 3 weeks), data from 12 Wistar-Kyoto (WKY) and 10 spontaneously hypertensive (SHR) rats were compared with those obtained from 11 WKY and 10 SHR controls treated with the vehicle. Systemic and regional hemodynamics were determined in the conscious, unrestrained state using the reference sample microsphere method. Mean arterial pressure (MAP) decreased in SHR by 9% (183±4 to 167±4 mmHg; p < 0.05) but remained unchanged in WKY, while cardiac index (CI) tended to decrease in both strains; heart rate fell by 15% only in WKY (481·;10 to 354·13 beats/min; p < 0.05). Total peripheral resistance index (TPRI) tended to decrease in SHR but to increase in WKY. Organ blood flow in SHR decreased in skin and splanchnic organs, while organ vascular resistance decreased in brain and increased in splanchnic organs. In contrast, organ blood flow increased in heart and decreased in kidneys and skin of the WKY, while organ vascular resistance decreased in heart and increased in kidneys and skin. Thus, diltiazem produced nonuniform and different hemodynamic effects in the two strains. Further, diltiazem did not alter the cardiac mass in either rat strain. We therefore conclude that diltiazem demonstrated a mild hypotensive effect in SHR that was associated with slight reductions in CI and TPRI, the latter being non-uniformly distributed in the component organ circulations.     

Hemodynamic comparison of diltiazem and TA-3090 in spontaneously hypertensive and normal Wistar-Kyoto rats

Systemic and regional hemodynamic effects of 2 benzothiazepine derivatives, diltiazem and its congener TA-3090, were studied both acutely and chronically in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. All hemodynamic data were obtained in the conscious state using the reference sample radiomicrosphere method. Mean arterial pressure was reduced significantly with both immediate and more long-term treatment with both drugs in the SHR. The hypotensive action of TA-3090 was about 3 times as potent as diltiazem. The pressure reduction with both drugs was associated with a decrease in total peripheral resistance. TA-3090 seemed to have lesser effect on heart rate than diltiazem, although its net effect on cardiac output was similar, remaining unchanged in each study group. After intravenous injection, both diltiazem and TA-3090 significantly reduced vascular resistances of the major target organs of hypertension: heart, brain and kidneys in SHR. However, with prolonged treatment, organ vascular resistances seemed to be nonuniformly distributed. Intrarenal hemodynamics revealed significant differences between SHR and WKY rats after intravenous diltiazem and prolonged treatment with TA-3090. Thus, efferent as well as afferent arteriolar resistance decreased and therefore calculated glomerular capillary hydrostatic pressure decreased in SHR; however, efferent resistance and glomerular pressure remained unchanged in WKY rats. In contrast, intravenous TA-3090 evoked no such differences. Thus, diltiazem as well as TA-3090 dilated efferent as well as afferent arterioles in the SHR but not in the WKY rats. This effect was associated with a reduction in glomerular capillary pressure, preventing glomerular hyperfiltration through efferent arteriolar dilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats

The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial and coronary vascular function and structure. Twelve-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with and without 12 weeks of vasodilator antihypertensive treatment (hydralazine) were studied using an isolated perfused rat heart model. Hydralazine treatment normalized blood pressure in SHR but did not cause regression of cardiac hypertrophy (heart weight to body weight ratio of SHR + hydralazine 4.33 +/- 0.098 vs. SHR 4.66 +/- 0.091; WKY 3.21 +/- 0.092 and WKY + hydralazine 3.38 +/- 0.152; mean +/- SEM). Coronary flow reserve, elicited by adenosine vasodilation in the perfused heart, was decreased in SHR (29%) compared with WKY (105%) and WKY + hydralazine (100%) and was significantly improved in SHR + hydralazine (75%). Morphometric evaluation of perfusion-fixed coronary arteries and arterioles (30-400 microns diameter) demonstrated a significant increase in the slope of the regression line comparing the square root of medial area versus outer diameter in SHR (0.444) compared with WKY (0.335) and WKY + hydralazine (0.336, p less than 0.05). Blood vessels from SHR + hydralazine were not different from control (0.338). Cardiac oxygen consumption was decreased in SHR (10.9 +/- 0.74 mumols oxygen/min/g/60 mm Hg left ventricular pressure) compared with WKY (22.4 +/- 1.47) and WKY + hydralazine (23.4 +/- 1.90; p less than 0.01), while SHR + hydralazine was intermediate (16.0 +/- 1.60). These studies suggest that significant alterations in myocardial and coronary vascular structure and function occur in hypertension-induced cardiac hypertrophy. The coronary vasculature is responsive to blood pressure, independent of cardiac hypertrophy, although moderate coronary deficits do remain after chronic antihypertensive therapy.     

不同时期氯沙坦短暂治疗对自发性高血压大鼠心脏AT1受体、AT2受体表达的影响

目的 观察不同时期氯沙坦短暂治疗对自发性高血压大鼠(SHR)的血压变化及心脏AT1受体、AT2受体表达的影响,探讨血管紧张素Ⅱ 1型受体(AT1R)、血管紧张素Ⅱ2型受体(AT2R)在高血压发病机制中的作用,为早预防、早治疗高血压开辟新的途径.方法 选用4周龄SHR及京都Wistar大鼠(WKY),分成4组:氯沙坦4周...     

氯沙坦对自发性高血压大鼠阻力血管结构的影响

目的探讨氯沙坦（Losartan）对自发性高血压大鼠（SHR）阻力血管结构的影响,并观察在高血压血管壁增厚的过程中血管紧张素Ⅱ(AngⅡ)所起的作用。 方法采用6周龄雄性SHR20只,随机分为Losartan治疗组（SHRlos）和对照组（SHR）。另选同系雄性6周龄WKY鼠10只作为正常对照组。6周龄SHRlos给予Losartan30mg/kg/d,溶于饮水灌胃治疗17周。颈动脉插管,心电血流动力学监护仪测定动脉收缩压,应用计算机图象分析,计算血管壁腔面积比,用光镜和透射电镜观察SHR肠系膜动脉三级分支结构的变化;血浆放免法测肾素活性和AngⅡ含量。 结果（1）动脉收缩压（SBP）治疗结束后,SHR     

钾通道开放剂埃他卡林对钾通道基因SUR2、Kir6．1和Kir6．2的影响

目的探讨高血压病理状态下ATP-敏感性钾离子通道(KATP)基因表达的变化,以及抗高血压新药钾通道开放剂埃他卡林(iptakali m)的作用特征,探讨埃他卡林逆转心血管重构的分子机制。方法自发性高血压大鼠(SHR)分为埃他卡林治疗组和模型对照组,同时设正常血压大鼠为正常对照,12周后取心脏、主动脉和尾动脉等组织,提取总RNA,利用反转录-聚合酶链式反应(RT-PCR)研究KATP各亚型基因SUR2、Kir6.1和Kir6.2在转录水平的改变。结果高血压状态下的SHR心脏、主动脉平滑肌和尾动脉平滑肌组织中的SUR2、Kir6.2基因表达显著高于对照大鼠(WKY),12周给药治疗后这些过表达的基因显著降低,P<0·05vs未治疗SHR;3种组织中Kir6.1的表达均无显著性变化。结论埃他卡林具有逆转高血压引起的心脏、主动脉平滑肌和尾动脉平滑肌中过表达的SUR2和Kir6.2的作用,这可能与其逆转高血压心血管重构有关。     

Effects of Acetylcholine and Nitroprusside on Systemic and Regional Hemodynamics in Hypertensive Rats

This study was performed to investigate the in vivoeffects of acetylcholine, a stimulator of endogenous NO production, and nitroprusside, an exogenous NO-donor, on hemodynamics in the normotensive (WKY) and the hypertensive (SHR) rat. Anesthetized rats were given microspheres for the measurement of cardiac index (CI), total vascular resistance (TPRI), regional blood flow and vascular resistance. Infusion of acetylcholine (2 μg/kg/min) caused a marked decrease in TPRI by (?35±5%, ±SEM) in the WKY (n=8), whereas in the SHR (n=8) a less pronounced reduction was seen (?14±3%, p<0.01 between groups). CI increased by 27±9% in the WKY, but was unaltered in the SHR. Blood pressure decreased similarily (17–20%). Acetylcholine significantly increased blood flow by about 40% in the kidneys and the heart in the WKY, but had no significant effect in the SHR. Other tissues, such as skeletal muscle and cerebral tissues, showed no major changes. Infusion of nitroprusside (1μg/kg/min) reduced blood pressure by 5 to 10% in the strains. The regional effects of nitroprusside did not differ between the strains. In conclusion, the acetylcholine-induced vasodilation in the kidney and the heart was attenuated in the SHR compared to the WKY. These findings might suggest a difference in the endothelial response between the SHR and the WKY in some, but not in all, tissues