Effects of angiotensin II type 1 receptor antagonist on nitric oxide synthase expression and myocardial remodeling in Goldblatt hypertensive rats

We evaluated the effects of long-term treatment with TCV-116, an angiotensin II type 1 receptor antagonist, on endothelial-cell nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression in the left ventricle and its relation to myocardial remodeling in Goldblatt hypertensive rats. Two-kidney, one-clip Goldblatt hypertensive rats (RHR) were assigned either to a TCV-116 treatment group (RHR-TCV, n = 8, 3 mg/kg/day, subdepressor dose) or to a group without treatment (RHR-V, n = 7) after their kidneys had been clipped for 4 weeks. TCV-116 was administered to rats in the treatment group for 6 weeks, and age-matched sham-operated rats (ShC, n = 7) served as a control group. Blood pressure in RHR-V and RHR-TCV was similar and significantly higher than that in ShC. The eNOS mRNA and protein levels and NOS activity in the left ventricle was significantly decreased in RHR-V compared with ShC, and significantly increased in RHR-TCV compared with ShC and RHR-V. RHR-V demonstrated a significant increase in fibrosis factor (type I collagen) mRNA expression, perivascular fibrosis, and myocardial fibrosis. These parameters in the microvasculature were improved significantly by TCV-116. Subdepressor dose of TCV- 116 improved pathological myocardial changes in RHR, which may be due in part to an increased eNOS mRNA and protein expression and NOS activity in the left ventricle.     

天麻钩藤饮逆转自发性高血压大鼠心肌纤维化的作用及机制

目的探讨天麻钩藤饮对自发性高血压大鼠（SHR）心肌纤维化及AngⅡ、ALDO的影响。方法将24只8周龄随机分成3组：即天麻钩藤饮组（剂量为20 g/kg）、卡托普利阳性对照组（剂量为100 mg/kg）及高血压模型组（SHR组）,并设正常对照组（同周龄正常血压WKY大鼠8只）,实验期24周。比较各组收缩压、左室质量（LVW）及左室质量指数（LVI）、心肌胶原含量、血管周围胶原面积与管腔面积比例（PVCA）及心肌胶原容积分数（CVF）,并采用放射免疫法检测心肌组织及血浆内AngⅡ、ALDO含量。结果天麻钩藤饮可显著降低SHR收缩压、LVW及LVI、心肌胶原含量、PVCA及CVF、血浆及心肌局部AngⅡ、ALDO水平（P〈0.01）。结论天麻钩藤饮可降低血压,抑制左室肥厚及心肌纤维化,其作用可能与降低血浆和心肌组织局部ALDO、AngⅡ水平有关。     

GCIP-27对自发性高血压大鼠左心室结构影响的实验研究

目的观察GCIP-27连续给药对自发性高血压大鼠(SHR)左心室结构的影响。方法30只SHR随机分为5组。空白溶剂对照组、阳性对照氯沙坦组(6mg·kg-1)和GCIP-27(10、30、90μg·kg-1ip,bid)3组,另6只Wistar-Kyoto大鼠(WKY)作为正常对照组。药物干预8wk后,测定SHR收缩压(SBP)、心室重量指数,分别用光镜、透射电镜观察心肌结构;VG染色测定心肌间质胶原含量。结果用药后第2周开始,SHR各剂量组(GCIP-2710、30、90μg·kg-1)SBP明显低于空白对照组(P<0·05);心肌重量指数(HMI)和左心室肥厚指数(LVMI)均明显降低(P<0·05);心肌间质胶原面积(CA)、胶原含量(IOD)及胶原容积分数(CVF)均明显减少(P<0·01)。光镜及电镜显示GCIP-27能明显改善SHR的心肌病理改变及超微结构。结论GCIP-27能明显改善SHR的心脏结构,降低心肌间质胶原增生,同时发挥降血压作用,进而对SHR左室重构的形成发挥干预及保护作用。     

血脂康对自发性高血压大鼠心肌重构的作用及其可能机制

目的观察血脂康(Xuezhikang,XZK)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)左室肥厚和心肌间质纤维化的影响,探究其可能机制。方法 30只SHR,♂,随机分为3组,血脂康(300 mg.kg 1.d 1)治疗组(XZK组,n=10),辛伐他汀(5 mg.kg 1.d 1)治疗组(SIM组,n=10),SHR对照组(SHR组,n=10),同时入组同龄Wistar-Kyoto大鼠为正常对照组(WKY组,n=10),均予等容量0.9%生理盐水灌胃。12周后,分离心脏,左室称重并计算左室重量指数(LVWI),心肌组织固定包埋后Masson染色并计算心肌胶原容积分数(CVF)及心肌血管周围胶原面积(PVCA),测定血清Ⅰ型前胶原羧基末端前肽(PⅠCP)浓度、心肌组织超氧歧化酶(SOD)活性及丙二醛(MDA)浓度。结果与SHR组相比,XZK组和SIM组可以显著降低LVWI(P<0.05)、CVF(P<0.01)、PVCA(P<0.01)及血清PⅠCP浓度(P<0.01),但SOD活力及MDA浓度差异无统计学意义。结论血脂康能够显著减轻SHR的左室肥厚,降低心肌间质纤维化程度,并与血压和胆固醇水平的变化无关,血脂康表现出与辛伐他汀相同的抗心肌重构作用,作用机制可能与心肌SOD活性和MDA浓度相关不大。     

Effect of chronic apocynin treatment on nitric oxide and reactive oxygen species production in borderline and spontaneous hypertension

The purpose of this study was to investigate the effect of NAD(P)H oxidase inhibitor – apocynin (4-hydroxy-3-methoxyacetophenone) on the increase of systolic blood pressure (SBP) in borderline (BHR) and spontaneously hypertensive rats (SHR). Young 6-week-old male BHR (offspring of SHR dams andWistar Kyoto sires) and SHR were treated with apocynin (30 mg/kg/day) for six weeks. SBP was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity was determined in the left ventricle and aorta. Protein expression of nuclear factor kappa B (NF-κB) and NAD(P)H oxidase subunits p67phox and p22phox as well as concentration of cGMPwere determined for the left ventricle. Apocynin significantly decreased SBP in all groups investigated. Administration of apocynin had no effect on NOS activity in either tissue studied. However, apocynin decreased protein expression of NF-κB (p65) and NAD(P)H oxidase subunit p22phox in both hypertensive groups and p67phox subunit in the SHR group. Moreover, apocynin was able to prevent a decrease in cGMP concentration in the left ventricle of both hypertensive groups. In conclusion, our study demonstrated that apocynin treatment partially prevented SBP rise in borderline and spontaneously hypertensive rats, yet without increasing activity of NOS in the left ventricle and aorta. However, apocynin was able to decrease production of reactive oxygen species in hypertensive rats; thus preventing the decrease in cGMP formation.     

培哚普利,普萘洛尔与双氢氯噻嗪对自发性高血压大鼠心血管结？…

AIM: To investigate the effects of perindopril, propranolol, and dihydrochlorothiazide on artery wall thickening, left ventricular hypertrophy, and cardiac fibrosis in spontaneously hypertensive rats (SHR). METHODS: After measurement of systolic blood pressure (SBP), 16-wk-old Male SHR were randomly divided into 3 groups (each n = 10), given perindopril (Per, 5 mg.kg-1.d-1), propranolol (Pro, 40 mg.kg-1.d-1), dihydrochlorothiazide (DCT, 100 mg.kg-1.d-1) respectively by gavage for 12 wk. Sex-, age-, and number-matched untreated SHR and normotensive Wistar Kyoto rats (WKY) served as controls. When the treatment finished, body weights (BW) and SBP were measured before decapitation of the rats. The heart was excised rapidly, the left ventricle was weighed and then subjected to collagen content analysis. Vascular wall and lumen ratio from aorta, renal arteries and branch III vessels of mesenteric arteries were determined morphometrically. RESULTS: Treated rats in 3 groups showed a lower SBP and the ratio of left ventricle weight to body weight (LVW/BW) compared with WKY. Artery wall thickening was similarly inhibited in the treated groups. Per and Pro inhibited cardiac fibrosis, but collagen concentration increased in DCT treated SHR [collagen volume fraction (CVF): 19 +/- 4 vs SHR 14 +/- 4, P < 0.05; perivascular collagen fraction(PVCF): 84 +/- 7 vs SHR 79 +/- 5, P < 0.05]. CONCLUSION: Per and Pro inhibited, but DCT promoted, cardiac fibrosis.     

沙库巴曲缬沙坦通过逆转高血压大鼠心房结构重塑降低房颤易感性

目的观察沙库巴曲缬沙坦(sacubitril/valsartan,Sac/Val,LCZ696)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)心房结构重构及房颤(atrial fibrillation,AF)易感性的影响。方法24只7周龄,♂,SHR随机均分为SHR组,SHR+Val组(30 mg·kg^-1·d^-1)和SHR+Sac/Val组(60 mg·kg^-1·d^-1),分别给予缬沙坦和沙库巴曲缬沙坦治疗,8只Wistar大鼠作对照组。快速起搏心房观察不同药物处理组SHR电生理指标及AF的可诱发性。Western blot检测肾素-血管紧张素系统(renin-angiotensin system,RAS)和纤维化相关蛋白的表达。结果与Wistar大鼠相比,SHR组AF诱发率明显增加(P<0.05);左房组织中ACE-1、angiotensin蛋白表达明显上调(P<0.05),ACE2下调(P<0.05);Col1A1、Col3A1、TGF-β、MMP-9均明显上调(P<0.05)。缬沙坦和Sac/Val治疗后均可明显逆转上述检测指标,且以SHR+Sac/Val组改善效果更明显(P<0.05)。结论缬沙坦和沙库巴曲缬沙坦均可通过抑制RAS改善SHR左心房纤维化,降低房颤易感性,且沙库巴曲缬沙坦效果优于缬沙坦,有望成为新的房颤治疗药物。     

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.     

Effect of long-term isradipine treatment on the hypertension-dependent changes in coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the effect of long-term isradipine treatment on the morphology of different-sized coronary artery branches in spontaneously hypertensive rats (SHR). Male SHR (12-week-old) received 1 mg/kg/day isradipine or vehicle (control group) orally for 12 weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as a reference group and did not receive any treatment. The animals were perfused with a fixative solution through the left ventricle and left ventricle blocks were embedded in resin. Sections including different-sized coronary artery branches were examined under a light microscope connected with an image analyser. The area occupied by the medial layer and the wall-to-lumen ratio were assessed in coronary artery branches of small (diameter less than 100 microns), medium (diameter 100-250 microns) and large (diameter greater than 250 microns) size. In control SHR, the blood pressure values and morphometric parameters examined significantly increased (p less than 0.001) in comparison with normotensive WKY rats. Isradipine treatment normalized blood pressure values in SHR and significantly reduced the area occupied by the medial layer and the wall-to-lumen ratio in small and medium-sized, but not in large-sized, coronary artery branches. These results indicate that isradipine treatment is able not only to reduce blood pressure elevation in SHR, but also to counteract the hypertension-dependent changes in the morphology of arterial branches controlling coronary resistances.     

卡托普利早期治疗自发性高血压大鼠抑制左室肥厚和c-myc表达而不影响c-fos表达(英文)

目的:探讨早期卡托普利治疗抑制左室肥厚的机制.方法:♂SHR宫内期给药(100 mg·kg~(-1)·d~(-1))到16周,40周处死,测定收缩压,左室重与体重比,左室c-myc和c-fos表达量(Northern杂交).结果:治疗明显降低血压,停药后24周,仍维持较低血压(20.9±1.2vs对照SHR 28.3±1.3 kPa,P<0.01)并抑制左室肥厚,心肌c-myc表达明显减少(0.57±0.13 vs对照SHR 2.07±0.16,c-myc mRNA/18S rRNA,P<0.01),c-fos表达无变化.结论:卡托普利持久地阻止高血压形成,抑制左室肥厚.后者可能是抑制c-myc表达结果,治疗不改变c-fos表达.     

Cilazapril prevents the development of cardiac hypertrophy and the decrease of coronary vascular reserve in spontaneously hypertensive rats

Cilazapril is a new inhibitor of angiotensin converting enzyme which has been shown to prevent development of high blood pressure and cardiac hypertrophy in spontaneously hypertensive (SHR) rats. The goal of the present experiment was to evaluate the effects of a chronic treatment with cilazapril on the decrease of coronary reserve in SHR rats. For this purpose, a group of 10 SHR rats which received by oral gavage 10 mg/kg/day of cilazapril for 9 weeks was compared with a control group of 9 SHR rats which received distilled water. Coronary reserve was evaluated by measuring coronary blood flow with the radioactive microspheres method before and after a dose of dipyridamole (2 mg/kg/min) which induces maximal coronary vasodilation. The left ventricular weight/body weight ratio was decreased in the cilazapril group compared to the placebo-treated group (p less than 0.001). Moreover, minimal coronary vascular resistance of the left ventricle and the right ventricle were 33% and 39%, respectively, lower in the cilazapril group as compared with the control group (p less than 0.01). We conclude that chronic treatment with cilazapril can prevent the development of left ventricular hypertrophy and the decrease of coronary vascular reserve in the left and right ventricles of spontaneously hypertensive rats.     

依那普利对肾性与自发性高血压大鼠左心室Eno1及GSTM2表达的影响

目的观察依那普利对肾性与自发性高血压大鼠左心室α-烯醇化酶(α-enolase,Eno1)及谷胱甘肽-s-转移酶,μ2(glutathione-s-transferase,μ2,GSTM2)表达的影响。方法实验共分5组:(1)对照组;(2)两肾两夹高血压大鼠组;(3)两肾两夹高血压大鼠+依那普利组;(4)自发性高血压大鼠组;(5)自发性高血压大鼠+依那普利组。检测各组大鼠血压及左室重量指数,行超声心动图检查,并运用Western blot检测各组大鼠左心室Eno1、GSTM2及β-肌球蛋白重链(β-myosin heavy chain,β-MHC)的表达情况。结果两肾两夹及自发性高血压大鼠血压与左室重量指数均明显高于对照组,依那普利治疗后,其左心室肥厚均得到明显逆转。与两肾两夹组相比,Eno1在自发性高血压大鼠中的表达明显上调;与对照组相比,GSTM2在自发性高血压大鼠中的表达明显下调,而两肾两夹组无变化,经依那普利治疗后,二者的表达变化均未得到明显逆转;β-MHC在两种模型中的表达均上调,而依那普利治疗后,β-MHC在二者中的表达均明显下调。结论依那普利能明显逆转β-MHC在两种模型中的差异表达,但不能逆转Eno1和GSTM2在二者中的差异表达。     

Chronic inhibition of farnesyl pyrophosphate synthase attenuates cardiac hypertrophy and fibrosis in spontaneously hypertensive rats

Farnesyl pyrophosphate synthase (FPPS), an essential enzyme in the mevalonate pathway, was reported to be upregulated in young spontaneously hypertensive rats (SHR) when compared with Wistar-Kyoto (WKY) rats, and this was accompanied by development of left ventricular hypertrophy. Five-week-old rats were daily gavaged with vehicle or an FPPS inhibitor (alendronate, 1 or 10 mg/kg) and blood pressures was monitored by the tail-cuff method every other week. Twelve weeks of alendronate treatment attenuated the left ventricular weight to body weight ratio (LVW/BW), hydroxyproline content, collagen deposition in the interstitia, and gene expression of atrial natriuretic peptide, B-type natriuretic peptide, and procollagen type I/III in the SHR left ventricle, all of which were significantly higher in SHRs than in WKY rats. Furthermore, long-term treatment with an FPPS inhibitor significantly reduced RhoA activation, ERK phosphorylation, and TGF-β1 expression in the SHR left ventricle, all of which were upregulated more in SHRs than in WKY rats. In conclusion, chronic treatment with an FPPS inhibitor attenuates the development of cardiac hypertrophy and fibrosis, and the suppression of ERK1/2 phosphorylation and TGF-β1 expression with inhibition of RhoA activation may be an important mechanism.     

越桔原花青素对大鼠心肌纤维化作用的影响

目的探讨越桔原花青素(procyanidin from Vaccini-um,PC)对大鼠心肌纤维化作用的影响及其机制。方法体内实验以异丙肾上腺素(isoprenaline,Iso)5 mg.kg-1.d-1背部皮下注射,构建大鼠心肌纤维化模型,同时以灌胃方式给予PC 100、200、400 mg.kg-1.d-1,分光光度法检测左心室心肌组织中羟脯氨酸(hydroxyproline,Hyp)、丙二醛(ma-londialdehyde,MDA)含量和超氧化物歧化酶(superoxide dis-mutase,SOD)活性;电镜观察心肌超微结构变化。体外实验采用细胞培养技术以血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)建立新生大鼠心肌成纤维细胞(cardiac fibroblast,CFb)增殖模型,给予25、50和100 mmol.L-1的PC干预。采用四唑盐(MTT)比色法测定细胞增殖;ELISA法测定Ⅰ、Ⅲ胶原及转化生长因子β1(TGF-β1)蛋白的含量。结果PC可剂量依赖性地降低心肌组织中Hyp、MDA含量、增强SOD活性,同Iso组比较差异有统计学意义(P<0.05或P<0.01),电镜结果显示:PC可缓解Iso所导致的心肌损伤。体外实验部分PC(25、50和100 mg.L-1)可抑制AngⅡ诱导的CFb增殖、胶原合成增加及TGF-β1蛋白含量增多,与AngⅡ组比较差异具有统计学意义(P<0.05或P<0.01)。结论PC可通过抗氧化作用,抑制CFb的增殖及胶原的合成,进而抑制大鼠心肌纤维化,对心肌具有一定的保护作用。     

灯盏花素对异丙肾上腺素引起大鼠心肌肥厚和纤维化的保护作用

目的研究灯盏花素(breviscapine,Bre)对异丙肾上腺素引起大鼠心肌肥厚和纤维化的保护作用及其机制。方法用异丙肾上腺素(isoproterenol,Iso)皮下注射,连续7d,建立大鼠心肌肥厚和纤维化模型。造模d2起给大鼠腹腔注射Bre12.5和25mg·kg-1·d-1,连续用药14d,测量大鼠心脏重量指数(HW/BW)和左心室重量指数(LVW/BW),放射免疫分析法检测左心室心肌组织中血管紧张素Ⅱ(AngⅡ)的变化;分光光度法检测左心室心肌组织中羟脯氨酸、一氧化氮(NO)含量和Na+,K+ATPase,Ca2+ATPase活性。结果Iso模型组大鼠心重指数和左心室重量指数明显增大,左心室心肌组织中AngⅡ和羟脯氨酸含量增高,NO水平下降,Na+,K+ATPase和Ca2+ATPase活力下降,Bre能提高心肌组织中的NO含量,抑制AngⅡ产生,增强Na+,K+ATPase和Ca2+ATPase活力,降低羟脯氨酸含量,抑制胶原的产生。结论Bre对Iso引起大鼠心肌肥厚和纤维化具有一定的改善作用。     

Effect of different dihydropyridine-type Ca2+ antagonists on left ventricle hypertrophy and coronary changes in spontaneously hypertensive rats

Effects of treatment with equi-hypotensive doses of first-, second-, and third-generation dihydropyridine-type Ca2+ channel blockers on hypertension-dependent left ventricle hypertrophy and coronary vascular changes were assessed in spontaneously hypertensive rats (SHRs) by quantitative microanatomic techniques. Male SHRs were treated for 12 weeks with equi-hypotensive doses of nifedipine, isradipine, manidipine, amlodipine, and lercanidipine. Untreated age-matched normotensive Wistar-Kyoto rats were used as a reference group. Compounds investigated decreased to a similar extent systolic pressure in SHRs. Increased cardiocyte size (hypertrophy), development of necrosis and fibrosis areas, and increased thickness of coronary arteries with luminal narrowing were observed in control SHRs. Pharmacologic treatment countered hypertension-dependent left ventricle and coronary artery changes in SHRs. Manidipine, amlodipine, and lercanidipine displayed a similar activity, whereas nifedipine and isradipine were less potent. These findings support observations that antihypertensive treatment counters hypertension-related left ventricle and coronary changes. The observation of a different effect of Ca2+ antagonists tested suggests the possibility of a more favorable cardiac profile exerted by some dihydropyridines. The evaluation of specific properties of dihydropyridines on hypertensive end-organ damage may contribute to better choices depending on clinical situations.     

CARDIAC HYPERTROPHY IN DIABETIC SPONTANEOUSLY HYPERTENSIVE RATS: ROLE OF ANGIOTENSIN II?

1. In the present study the role of angiotensin II (AngII) in the development of cardiac hypertrophy in diabetes combined with hypertension was investigated. 2. Diabetes was induced in 8-week-old male spontaneously hypertensive rats (SHR) by intravenous injection of streptozo-tocin (45 mg/kg body weight). Diabetic SHR were treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril at a dose of 0.4 mg/kg per day. 3. Twelve weeks following the onset of diabetes, hearts were arrested in diastole and were perfusion-fixed. The right ventricle and left ventricle plus septum were weighed and the volume of the ventricular walls was determined using the Cavalieri principle. 4. Induction of diabetes in SHR led to a significant reduction in bodyweight compared with non-diabetic control SHR and this was not affected by ramipril treatment The development of hypertension was not as great in diabetic SHR compared with controls, such that at 12 weeks following the onset of diabetes systolic blood pressures (SBP) averaged 191 ± 3 and 230 ± 4 mmHg in diabetic SHR and controls, respectively. Ramipril treatment significantly lowered SBP in diabetic SHR. 5. The left ventricle plus septum volume:bodyweight ratio (LV vol:BW) was significantly higher in diabetic SHR compared with controls (3.83 ± 0.19 and 3.26 ± 0.16 mm³/g, respectively). Ramipril treatment did not affect growth of the left ventricle in diabetic SHR with the LV vol:BW ratio averaging 3.95 ± 0.14 mm³/g. Similar trends on growth were observed in the right ventricle. 6. In conclusion, the development of cardiac hypertrophy in diabetic SHR appears to occur by mechanisms independent of AngII and the elevation of blood pressure.     

Beneficial effect of atorvastatin on left ventricular remodeling in spontaneously hypertensive rats

This study was designed to investigate whether atorvastatin has a beneficial effect on left ventricular (LV) remodeling in spontaneously hypertensive rats (SHR), and then explore the underlying mechanisms involved. 12 SHRs were randomized to receive either distilled water (SHR group, n = 6) or atorvastatin (ATV group, n = 6) for 10 weeks. Age-matched Wistar-Kyoto rats (WKY) gavaged by distilled water were used as normal controls (WKY group, n = 6). By using these rats, we observed the effects of atorvastatin on LV hypertrophy and fibrosis, and investigated atorvastatin-induced cell apoptosis and p27 protein expression. In addition, the serum lipid concentration and blood pressure level were also measured in this study. 10 weeks later, a significant decrease in the cardiosomatic ratio, LV weight to body weight ratio and cardiomyocyte transverse diameter, as well as myocardial hydroxyproline and collagen content was observed in the atorvastatin-treated SHR. In addition, atorvastatin increased the positive rate of cell apoptosis and p27 protein expression. A decreased serum lipid concentration and a reduced systolic blood pressure level were also found in the atorvastatin-treated SHR. These findings demonstrated a beneficial effect of atorvastatin on adverse LV remodeling in SHR, and the induction of cell apoptosis and upregulation of p27 protein may serve as the underlying mechanisms of this action.     

粉防己碱抑制自发性高血压大鼠心肌纤维化

目的：观察粉防己碱对自发性高血压大鼠心肌胶原和心肌僵硬度的作用。方法：测定羟脯氨酸表示胶原的量，胃酶抽提法和ＳＤＳ－ＰＡＧＥ方法测定胶原Ⅰ／Ⅲ型比例，离体灌注大鼠心脏测定左室心肌舒张僵硬度。结果：粉防己碱显著降低心肌胶原浓度和含量，降低胶原Ⅰ／Ⅲ型比例，改善心肌舒张僵硬度。结论：粉防己碱因其有效的抗纤维化作用，能逆转心肌舒张功能障碍。     

盐酸埃他卡林对高血压心脏重构的作用

目的　在自发性高血压大鼠 (spontaneouslyhyperten siverat,SHR)和脑卒中易感型自发性高血压大鼠 (stroke pronespontaneouslyhypertensiverat,SHRsp)上 ,评价盐酸埃他卡林 (iptakalimhydrochloride ,Ipt)对高血压心脏重构的实验治疗学作用。方法　SHR于第 12周龄进入实验 ,赖诺普利 (lisinopril,Lis) 12mg·kg-1,Ipt 3mg·kg-1灌胃每天 1次 ,连灌 4wk ;SHRsp于第 11周龄进入实验 ,实验设Ipt0 2 5、1和 4mg·kg-13个剂量组及溶剂对照组 ,灌胃给药每天 1次 ,持续给药 12wk ,观察药物对高血压心脏重构的影响。结果　实验期 4wk内 ,SHR对照组血压和心率进行性增高。Ipt能有效控制SHR的血压 ,降压效果确切 ,且可抑制SHR心率加快的趋势 ,但对SHR高血压心脏重构无明显作用。相同实验条件下 ,Lis也能有效控制SHR的血压 ,降压效果确切 ,对心率无明显影响 ;Lis治疗可减轻SHR高血压心脏重构。实验期 12wk内 ,SHRsp溶剂对照组血压持续性进行性增高。Ipt 3个剂量组均能降低SHRsp血压 ,Ipt 4mg·kg-1组在给药后第 4周开始出现心率减低。Ipt 3个剂量组的左心室和室间隔 (LV +S)重量及其与体重的比值[(LV +S) /BW ]低于溶剂对照组。 4组动物之间的右室重量(RV)均无差异。结论　Ipt能有效地控制SHR和SHRsp的血压 ,其对