Role of benazepril on extracellular signal-regulated kinase activity and expression of B-type natriuretic peptide in spontaneously hypertensive rats

AIM：To investigate the role of benazepril on extracellular signal-regulated kinase (ERK) activity and expression of B-type natriuretic peptide in spontaneously hypertension rat (SHR).METHODS：Wistar Kyoto rats were used as control group.Twenty one 14-week-age SHR were randomized into 3 groups,7 rats each：benazepril group (10 mg·kg-1·d-1);hydralazine group (10 mg·kg-1·d-1) and sham group.In each group drugs or equal volume of vehicle (0.5% carboxymethyl cellulose) were administered respectively for 10 weeks by gavage.The ratio of left ventricle weight to body weight （LVW/BW） was measured to reflect myocardial hypertrophy.The caudal arterial pressure was measured by tail-cuff.Protein expression of p-ERK in myocardial tissue was detected by Western blotting,BNP mRNA in myocardial tissue was examined by RT-PCR,and protein expression of plasma BNP was detected by ELISA.RESULTS：1.Benazepril and hydralazine lowered the blood pressure after 10 weeks treatment (P<0.01).2.The ratio of LVW/BW in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).3.The protein expression of p-ERK in myocardial tissue in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).There was no significant difference of p-ERK expression between SHR hydralazine group and SHR sham group (P>0.05).4.The levels of plasma BNP and BNP mRNA in myocardial tissue in SHR benazepril group were significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).There was no significant difference of plasma BNP and BNP mRNA in myocardial tissue between SHR hydralazine group and SHR sham group (P>0.05).CONCLUSIONS：Benazepril inhibited ERK activation,resulting in regression of myocardial hypertrophy and accompanied by the reduction of BNP level.However,in spite of the effect of lowering blood pressure,hydralazine did not prevent or regress cardiac hypertrophy and did not decrease the level of p-ERK and BNP in SHR.BNP level might serve as a therapeutic index for reversal of myocardial hypertrophy.     

Alterations in gene expression of sarcoplasmic reticulum Ca2+-ATPase and phospholamban detected by RNA array in spontaneously hypertensive rats

AIM: To explore the relationship between the alteration in gene expression of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) and phospholamban (PLB) in spontaneously hypertensive rats (SHR). METHODS: 294 samples of total RNA were obtained from the tissue of ventriculum , aortic smooth muscle, liver and kidney in SHR and normotensive rats (WKY). RNA array was used to determine the mRNA levels of SERCA and PLB. RESULTS: Compared with age-matched WKY rats, the systolic blood pressure increased higher in 6-week-old SHR (P<0.01). The cardiosomatic ratio was significantly higher in 10-week-old SHR (P<0.01), in cardiac sarcoplasmic reticulum, the mRNA levels of SERCA were significantly increased from 4 weeks (P<0.05 or P<0.01). In the aortic sarcoplasmic reticulum, the mRNA levels of SERCA were significantly increased from 4 weeks to 12 weeks (P<0.05 or P<0.01). There was no significant change in the expression of PLB between the two groups. The ratio of cardiac SERCA and PLB was significantly increased since 6-week-old (P<0.05 or P＜0.05)in SHR. The ratio of aortic SERCA and PLB in SHR was significantly increased since 4-week-old (P<0.05 or P<0.01) vs WKY. CONCLUSION: Our results provided the evidence that the abnormalities of intracellular Ca²⁺ hemostasis in SHR represent the progressive nature of essential hypertension.     

Pathogenesis of early cardiac myocyte damage after severe crush injury

AIM:To study the changes of plasma atrial natriuretic peptide(ANP), endothelin-1 (ET-1) and serum cardiac troponin I(cTnI) levels and the effects of ANP and ET-1 on myocardium in crush injury rats.METHODS:Crush injury was produced in SD rats,the serum levels of cardiac enzyme and cardiac troponin I,plasma levels of ANP and ET-1 were studied by automated biochemical analyzer,automated chemiluminescence assay and radioimmunoassay. RESULTS:The plasma ET-1 level was much lower,the levels of plasma ANP and serum cardiac enzyme and cTnI were much higher after crush injury than those of the control group(P＜0.05).CONCLUSION:ANP and ET-1 may play an important role in cardiomyocyte injury in the early stage of crush injury.     

Changes and clinical implications of plasma ANP,BNP and CNP levels in type 2 diabetic patients with vascular complications

AIM:To examine the changes and clinical implications of the plasma atrial natriuretic peptide (ANP), brain natriuretic peptide(BNP) and C-type natriuretic peptide(CNP) levels in type 2 diabetic patients with vascular complications. METHODS:9 subjects without diabetes, 34 diabetic patients without vascular complications and 23 diabetic patients with vascular complications were enrolled in the study and categorized into three groups. Plasma proANP, BNP fragment and N-terminal pro-CNP (NT-proCNP) were measured by enzyme linked immunosorbent assay (ELISA). The changes and associations of the plasma natriuretic peptide levels among three groups were analyzed. RESULTS:Compared with those in the controls and diabetics without vascular complications, the plasma proANP and BNP fragment levels in diabetic patients with vascular complications increased significantly (P<0.01). However, the plasma NT-proCNP level in this group decreased significantly (P<0.01). Nevertheless, no significant differences in the plasma proANP, BNP fragment and NT-proCNP levels among three subgroups (diabetics patients with macrovascular and/or microvascular complications) were observed (P>0.05). The plasma ANP level of diabetic patients with vascular complications was corelated significantly with the BNP levels (r=0.309, P<0.05). Furthermore, the ANP and BNP levels were correlated significantly with the CNP level (r=-0.374, P<0.05; r=-0.653, P<0.01). CONCLUSION:Measurement of the plasma ANP, BNP and CNP levels together may be a simple, cost-effective and reliable way to screen for diabetic patients with vascular complications.     

Effect of atrial natriuretic peptide on acute lung injury induced by lipopolysaccharide

AIM: To investigate effect of atrial natriuretic peptide (ANP) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rat. METHODS: Mean arterial blood pressure (MAP) was recorded with model 6280 physiology intelligentialize grapher, nitric oxide (NO) and endothelin (ET) concentrations in plasma were measured after lipopolysaccharide (LPS) or following LPS ,ANP was injected into vein in rats. After experiment,lung water as well as pulmonary histopathological changes was measured and observed, respectively. RESULTS: Administration of LPS elicited a persistence decrease in MAP (8.1 kPa±2.6 kPa,at 4 h,P<0.01 vs control); NO and ET concentration in plasma was evident higher than that in control group, respectively (P<0.01); Wet-dry ratio of lung was higher than that in control group (5.15±0.43,at 4 h) (P<0.05); Alveolus detelectasis was observed and pulmonary mesenchyme was thicker than that in control group. No erythrocyte and leukocytes in alveolus,which show an interstitial pulmonary edema, was observed in LPS+ANP group, ANP maintained MAP at higher levels (13.35 kPa±2.93 kPa, at 4 h, P<0.05 vs LPS) after an transient decline when LPS was injected; NO and ET concentration of plasma had all significantly decrease, respectively (P<0.05 vs LPS, at 4 h); Wet-dry ratio of lung was lower than LPS group (4.57±0.35, P<0.05). Compared with control group the ratio was not evident difference (P>0.05); The histopathological of lung displayed markedly improved. CONCLUSION: ANP attenuates ALI induced by LPS in the rat. The effect of ANP may be via decreasing secretion of ET,NO and regulation arterial blood pressure.     

Astragali radix extract ameliorates renal resistance to atrial natriuretic peptide in rats with experimental nephrotic syndrome

AIM: To study the effects of astragali radix extract (ARE) on renal resistance to atrial natriuretic peptide (ANP) in rats with experimental nephrotic syndrome. METHODS: Male Sprague-Dawley rats were randomly divided into normal control, adriamycin nephropathy (ADR), ADR treated with ARE (2.5 g· kg^-1· d^-1) and ADR treated with benazepril (10 mg· kg^-1· d^-1). After 6 weeks, rats received intravenous infusion of 2% body weight isotonic saline. Urinary cGMP excretion (U_cGMPV), plasma ANP level, renal PDE5 activity and protein expression were also detected. RESULTS: ARE increased U_NaV while ACEI was not natriuretic. Nephrotic rats had a blunted natriuretic response and reduced rate of U_cGMPV after volume expansion despite higher plasma ANP concentration. ARE increased U_cGMPV and restored partly natriuretic response to volume expansion. The activity and protein abundance of renal PDE5 were high in nephrotic rats. ARE significantly reduced the PDE5 activity and protein expression. CONCLUSION: ARE may ameliorate the renal resistance to ANP in rats with adriamycin nephropathy by inhibiting the PDE5.     

The role of C-type natriuretic peptide in balloon injury of rat aorta

AIM and METHODS: In a model of balloon injury of rat aorta, the dynamic changes of C-type natriuretic peptide (CNP) in plasma and aortic tissues and the effect of exogenous CNP on intima/media (I/M) ratios were studied. RESULTS:CNP levels in plasma were significantly increased by 80.7% (P＜0.01),43.5%(P＜0.05) and 27.5% (P＜0.05) on 3 days, 10 days and 21 days after balloon injury, but its levels in aortic tissues were decreased by 46.6% (P＜0.05) on day 3 and increased by 2.8 (P＜0.01),1.6(P＜0.05) and 0.82-fold (P＜0.05) on day 10, day 21 and day 28 after balloon injury of rat aorta. Result also showed that the administration of CNP i.p. inhibited neointima formation. I/M ratios were decreased by 23% (P＜0.05) and 20% (P＜0.05) on 7 days, 21 days after balloon injury of rat aorta.CONCLUSION:CNP might be involved in the process of recovery after vascular endothelium-denudation and exogenous CNP suppress the neointima formation.     

Changes of plasma and myocardial calcitonin gene-related peptide in myocardial stunning rats

AIM: To investigate changes of calcitonin gene-related peptide(CGRP) in myocardial stunning rats. METHODS: Rat in vivo myocardial stunning model was used. CGRP content in plasma and myocardium were determined by radioimmunoassay. RESULTS: Plasma level of CGRP increased significantly (P＜0.01), but in left ventricular myocardium CGRP decreased obviously (P＜0.05) in myocardial stunning group compared with the control group. CONCLUSION: CGRP content in the left ventricular myocardium was negatively correlated with plasma CGRP.     

The renal L-arginine/nitric oxide pathway and erythrocyte L-arginine transport in spontaneously hypertensive rats

AIM: To investigate the changes of the renal L-arginine /nitric oxide pathway and the relationship of L-arginine transport between kidney and erythrocytes in spontaneously hypertensive rat (SHR). METHODS: Sixteen week old SHR, 16 week old SHR with captopril (CAP) treated for four weeks and 16 week old WKY rats were used in the experiment. L-arginine transport, NO synthase(NOS) activity, nitrite and cyclic GMP (cGMP) content were measured in renal tissue or erythrocytes. RESULTS: In the renal tissue, compared with that of WKY group, the Vmax of high-or low-affinity L-arginine transporter, NOS activity, NO₂^- and cGMP content of SHR group were significantly decreased (P＜0.01 or P＜0.05). The Vmax of high-affinity L-arginine transporter and NOS activity of CAP group were significantly enhanced as compared with SHR group (+90%, P＜0.01; +58.6%, P＜0.05). The NOS activity had significant positive correlation with the Vmax of high-affinity L-arginine transporter (r=0.585, P＜0.05). The changes of erythrocyte L-arginine transport were the same as that of kidney. The Vmax of SHR group was lower than that of WKY group (-30%, P＜0.01), and the Vmax of CAP group was higher than that of SHR group (+26.5%, P＜0.01). Km was not significantly changed. There is a positive correlation between the Vmax of L-arginine transport in erythrocyte and the Vmax of high- or low-affinity L-arginine transporter in renal tissue, (r=0.8434, P＜0.01, high-affinity; r=0.5255, P＜0.05, low-affinity). CONCLUSION: There existed a functional inhibition in L-arginine/nitric oxide pathway in the kidney of SHR. It can be recovered obviously by captopril treatment. The changes of L-arginine transport in kidney coincide with that in erythrocyte.     

Positive inotropic action of urocortin on isolated heart tissues of the spontaneously hypertensive rat

AIM:To study the effects of urocortin (Ucn) on the isolated heart tissues of spontaneously hypertensive rat (SHR). METHODS:Effects of Ucn on contractile force and heart rate were observed in the SHR and Wistar rat right atrium, left atrium and right ventricle strip. RESULTS:Ucn (1-10 nmol/L) concentration-dependently increased the contractile force in the SHR and Wistar rat isolated right atrium. Ucn increased the contractile force in the SHR by (31.1±14.9)% at 3 nmol/L and by (65.7±22.4)% at 10 nmol/L, and its inotropic effect was significantly greater than that in Wistar rat (P<0.01) at the same concentration. Ucn (1-10 nmol/L) concentration-dependently increased the contractile force in the SHR and Wistar rat isolated left atrium, this effect had no difference between SHR and Wistar rat. No effect of Ucn on the heart rate of the isolated right atrium and on the contractile force of the isolated right ventricle strip was observed. CONCLUSION:The results indicate that the inotropic responses to Ucn in SHR are significantly greater than those in Wistar rats, suggesting that the change in heart function related with Ucn in SHR may have an important role in the pathophysiology of the hypertension.     

The inhibition of nitric oxide synthase for long time up-regulates vascular angiotensin Ⅱ receptor

AIM:To observe the effects of aortal angiotensin Ⅱ(AngⅡ)levels and AngⅡ receptor in the hypertensive rat models. METHODS: Intraperinoneal injection of L-N^ω-nitro-arginine(L-NNA) into rats induced hypertensive model, the binding of aortal AngⅡ receptor and the contents of aortal tissue AngⅡ and plasma NO₂^-+NO₃^-(NOx) were determined.RESULTS:Compared with the control group, the blood pressure of the rats treated with L-NNA was significantly increased by 142%(P＜0.01),the plasma NOx levels were decreased by 48%. However, in the rats treated for 4 weeks the ratio of cardial index was increased by 128%(P＜0.01),the plasma AngⅡ levels weren't significantly changed, the contents of vascular tissue AngⅡ were increased by 612%(P＜0.01) and the Bmax of [¹²⁵I]-AngⅡ was increased by six times (P＜0.01),the affinity was doubled respectively.CONCLUSIONS:Nitric oxide synthase (NOS) inhibition mostly influes the reninangiotensin system in regional tissue. The inhibition for long time up-regulates vascular AngⅡ and AngⅡ receptor, which can support the hypothesis "NOS inhibition can induce AngⅡ-depended hypertension".     

Immunohistochemical observation and imaging analysis of iNOS and vasoactive intestinal peptide in experimental diabetic rat lung

AIM: The pathological changes in inducible nitric oxide synthase (iNOS) and vasoactive intestinal peptide (VIP) in diabetic rat lung were investigated.METHODS: Using immunohistochemical method and imaging analysis, the changes in iNOS and VIP were observed in normal and diabetic rat lung. RESULTS: In diabetic rats, the iNOS positive or weak positive staining was localized in epithelial cells of bronchi, epithelial cells of alveolar ducts, alveolar sacs, and arteries, but negative in endothelial cells of vein and capillary. Image analysis showed the area, the integral absorbance(IA) and relative contents of iNOS were significant lower than that of control (P＜0.01, P＜0.01 and P＜0.01). In diabetic rats, the ciliated cells of bronchi epithelium showed VIP positive reaction, while the bronchial smooth muscle, surounding tracheobronchial submucosal glands, the tunica adventitia of pulmonary arteries, and alveolar septum were stained weak positive or negative for VIP. Image analysis showed the area, the IA and relative contents of VIP were significantly lower than those of control (P＜0.01, P＜0.01 and P＜0.01).CONCLUSION: The pathological changes in diabetic rat lungs are not only involving autonomic neuropathy but also NANC nerves. Nitric oxide and VIP, which are NANC neurotransmitter, may play an important role in pathogenesis of pathological change in diabetic lung.     

The regulation of nitric-oxide synthase/nitric-oxide system by endogenous carbon monoxide in rats with pulmonary hypertension

AIM:To study the role and the mechanism of heme oxygenas/endogenous carbon monoxide on nitric oxide synthase/nitric oxide system in rats with pulmonary hypertension induced by hypoxic hypercapnia.METHODS:Sprague-Dawley rats were randomly divided into three groups: control group (A group), hypoxic hypercapnic group (B group), hypoxic hypercapnia+hemin group (C group). Blood CO concentration (COHb%), NO concentration, HO-1 activity, iNOS, cNOS in blood serum and lung homogenate were measured, respectively. RESULTS:① mPAP and RV/(LV+S) of B group were significantly higher than those of A and C group(P＜0.01).② Blood CO concentration, activity of HO-1in blood serum and lung homogenate in rats of B group were significantly higher than those of A group, but were significantly lower than those of C group (P＜0.01). ③ NO concentration in blood serum and lung homogenate in rats of B group were significantly lower than those of A group, those of C group were significantly higher than those of B group (P＜0.01).④The activity of iNOS in blood serum and lung homogenate in rats of B group were significantly higher than those of A group, but were significantly lower than those of C group (P＜0.01). Activity of cNOS in blood serum and lung homogenate of B group were significantly lower than those of A group (P＜0.01), and there was no significant difference between cNOS in B and C group.CONCLUSION:Endogenous carbon monoxide upregulated iNOS/NO system in rats with chronic pulmonary hypertension induced by hypoxic hypercapnia.     

Effects of atorvastatin on expression of cytochrome P450 hydroaylase in spontaneously hypertensive rats

AIM: To investigate the effects of atorvastatin on blood pressure and expression of cytochrome P450 hydroaylase (CYP) 4A1 in spontaneously hypertensive rats (SHR). METHODS: SHRs (n=18) were randomly divided into three groups: SHR control group, 50 mg atorvastatin (HATV) group and 10 mg (LATV) group. Six male Wistar-Kyoto rats were selected as normal control group (WKY group). All rats were given vehicle once a day by gavage for 10 weeks. Systolic blood pressure (SBP) was measured before and after treatment every 2 weeks. The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney, and aorta were detected by RT-PCR and Western blotting analysis, respectively. Plasma lipids were also measured.RESULTS: SBP in all SHR groups was much higher than that in WKY group before experiment (P<0.01). Compared with SHR control group, SBP significantly decreased in HATV group at 6, 8, 10 weeks and in LATV group merely at 10 weeks (P<0.01 or P<0.05). The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney and aorta tissues of SHR control group were significantly higher than those in WKY group (P<0.01 or P<0.05). After 10 weeks, the levels of CYP 4A1 mRNA, protein and plasma lipids in HATV and LATV groups were markedly lower than those in SHR control group (P<0.01 or P<0.05).CONCLUSION: Atorvastatin down-regulates the expressions of CYP 4A1 mRNA and protein in SHR, which may be the mechanism of the favorable effects of statins on regulation of hypertension.     

Changes in L-arginine/NO pathway of erythrocytes in patients with essential hypertension

AIM:To investigate the changes of L-arginine/nitric oxide(L-Arg/NO) pathway and the characteristics of L-Arg transport in erythrocytes (RBC) in patients with essential hypertension(EH). METHODS: 12 EH patients were studied with 10 normotensive people as control. The nitric oxide (NO) production was assayed by measuring the nitrite in medium using Greiss reaction. NO synthase activity was measured according to the method described by Ghigo. In order to achieve zero-trans condition, erythrocytes were incubated at 37℃ for 3 h and then L- Arg transport of RBC were determined by measuring the influx of radiolabelled L-arginine by Deliconstantins described method. RESULTS: In EH patients, NO production was lower than that in control (P＜0.01) and the cGMP quantity was only 72.8% of control (P＜0.01). NOS activity of EH patients decreased to 47.8% of control. Saturable influx of L-Arg was mediated by the classical cationic amino acid transport system Y^＋ and Y^＋L system with high affinity. Under zero-trans condition, the ability of L-Arg transport by RBC in EH patient was lower than control. The V_max for total L-Arg transport and via system Y^＋ respectively decreased 36.8% and 42.5% compared with control. But V_max or L-Arg transport via system Y^＋L was not affected by EH. In EH patients K_m value for total, system Y^＋and system Y^＋L had no difference with control. CONCLUSION: The present study suggested that there is disturbance of L-Arg/NO pathway in human erythrocytes from patient with EH.     

Effect of puerarin on pulmonary arterioles wall collagen metabolism of chronic hypoxia hypercapnia rats

AIM:To investigate the effect of puerarin on pulmonary vessel collagen metabolism in pulmonary hypertension rats induced by chronic hypoxia and hypercapnia.METHODS:Collagen Ⅰ, Ⅲ and their mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization.RESULTS:① Light microscopy showed media thickness of pulmonary arterioles was much higher in HH(hypoxic-hypercapnia) group than that of NC(normal control) group, and, vessel cavity turned more straiter in HH group than that of NC group.However, the damage of pulmonary arterioles in HP(hypoxic-pueratin) group was much slighter than that of HH group. ② The levels of plasma ET-1 and lung homogenates Hyr were much higher in HH group than those of NC group(P＜0.01), and lower in HP group than HH groups(P＜0.01).Plasma NO content in group HH was lower than that of group NC(P＜0.01), it was higher in group HP than that of group HH(P＜0.01).③Expression of collagen Ⅰ and collagen Ⅰ mRNA in pulmonary arterioles were significantly higher in HH groups than those of NC group (P＜0.01), and they were lower in HP group than those of HH group (P＜0.01).Expression of collagen Ⅲ and collagen Ⅲ mRNA showed no difference among three groups(P＞0.05).CONCLUSION:Puerarin inhibited the deposition of collagen and improved pulmonary vessel remodeling.     

The effect of vasoactive substances on synthesis and release of C-type natriuretic peptide in cultured human endothelial cells

AIM:To investigate the effect of endothelin (ET), angiotensin II (AngII) and homocysteine (Hcy) on C-type natriuretic peptide (CNP) synthesis and release. METHODS: Human endothelial cell was cultured; CNP was measured by radioimmunoassay method. RESULTS: ET and AngII could augment CNP synthesis in human endothelial cells. Compared with control group, 10^-9,10^-8,10^-7 mol/L ET and Ang II increased CNP content of endothelial cells by 1%(P＞0.05), 49%(P＜0.05),117%(P＜0.01) and 137% (P＜0.01),165%(P＜0.01),201%(P＜0.01),respectively. A great dose of ET and Ang II also stimulated CNP release from cultured human endothelial cells. Hcy had no effect on CNP synthesis, but 10^-9,10^-8,10^-7 mol/L Hcy enhanced CNP release from cultured human endothelial cells by 17%(P＞0.05),84%(P＜0.01) and 555%(P＜0.01), respectively. CONCLUSION: ET, AngII and Hcy might be involved in the synthesis and release of human endothelial cell CNP.Fig 1 Time-course of CNP syntheis and release in cultured human endothelial cell ( ±s,n=6)     

Effect of atorvastatin on blood pressure in spontaneously hypertensive rats

AIM: To explore the mechanisms underlying the effect of atorvastatin on blood pressure in spontaneously hypertensive rats (SHR). METHODS: The effects of atorvastatin on plasma endothelin-1, aortic nitric oxide synthase, aortic smooth muscle cell (ASMC) apoptosis and p27 expression in SHR were evaluated. 12 eight-week-old SHR were randomized into atorvastatin group (ATV, n=6) and SHR group (n=6). 6 age-matched normotensive Wistar-Kyoto rats (WKY) were served as controls. 50 mg·kg-1·d-1 of atorvastatin was administered to ATV by gavage for 10 weeks. Serum cholesterol and triglycerides were measured, and systolic blood pressure of caudal artery was examined. Plasma endothelin-1 and nitric oxide synthase activity of aortic tissue were measured. ASMC apoptosis rate was detected by TUNEL technique, and positive expression rate of P27 in ASMC was analyzed. RESULTS: After 10 weeks, systolic blood pressure in ATV was significantly lower than that in SHR ［(134.17±3.60）mmHg vs （173.33±3.78）mmHg, P<0.01］. Compared with SHR, serum cholesterol and triglycerides were significantly lower (P<0.01, P<0.01) in ATV. Additionally，atorvastatin significantly decreased plasma endothelin-1 ［(130.04±40.07）ng/L vs （196.74±59.69）ng/L, P<0.05］ and increased nitric oxide synthase activity in aortic tissue ［(0.189±0.040）kU/g protein vs (0.124±0.057)kU/g protein, P<0.01］, compared with SHR. ASMC apoptosis rate was higher in ATV than that in SHR (16.94%±3.08% vs 9.01%±2.36%, P<0.01). Compared with WKY, positive expression rate of p27 in ASMC from ATV was higher (33.02%±5.01% vs 24.25%±4.41%, P<0.05), whereas that was lower in SHR (16.08%±7.09% vs 24.25%±4.41%, P<0.01). CONCLUSION: Atorvastatin may reduce the plasma endothelin-1， up-regulate nitric oxide synthase activity and ASMC P27 expression and facilitate ASMC apoptosis，which may effectively reduce blood pressure in SHR.