Alterations in sarcoplasmic reticulum and angiotensin II receptor type 1 gene expression in spontaneously hypertensive rat hearts

Left ventricular hypertrophy (LVH) is an adaptive change in response to hypertensive pressure overload. Some evidence indicates that the decrease in sarcoplasmic reticulum (SR) Ca2+-ATPase mRNA expression, which may contribute to a diastolic dysfunction of the heart, occurs in the experimental pressure overload model. Also, recent studies have demonstrated that angiotensin II (Ang II) and angiotensin II receptor type 1 (AT1) play important roles in LVH. The purpose of this study was to investigate the function of the SR and the role of AT1 in genetic hypertension in spontaneously hypertensive rats (SHR) at ages 10 and 18 weeks. In SHR, cardiac hypertrophy has already developed at 10 weeks of age. SR Ca2+-ATPase activity and mRNA expression were significantly lower in SHR than in Wistar-Kyoto rats (WKY). Plasma renin activity in SHR was unchanged compared with WKY, whereas the Ang II concentration in SHR was significantly higher than that in WKY. AT1 mRNA expression in SHR was similar to that in WKY. These results suggest that in the early stage of hypertension in SHR Ang II may stimulate hypertrophy in the cardiomyocytes through the AT1, which is not downregulated by a high concentration of Ang II.     

高血压左心室肥厚与血管紧张素Ⅱ受体的关系

目的探讨自发性高血压大鼠(SHR)左心室肥厚和血管紧张素Ⅱ(AngⅡ)受体的关系。 方法雄性SHR自10周龄始,给予依那普利［enalapril20mg/(kg     

Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

It has been suggested that proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, may function as a component of the tissue renin-angiotensin system (RAS). To investigate the role of proang-12 in the production of angiotensin II (Ang II), we measured its plasma and tissue concentrations in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, with and without RAS inhibition. The 15-week-old male WKY and SHR rats were left untreated or were treated for 7 days with 30?mg?kg(-1) per day losartan, an angiotensin receptor blocker, or with 20?mg?kg(-1) per day imidapril, an angiotensin-converting enzyme (ACE) inhibitor. Both treatments increased renin activity and the concentrations of angiotensin I (Ang I) and Ang II in the plasma of WKY and SHR rats, but neither affected plasma proang-12 levels. In contrast to the comparatively low level of proang-12 seen in plasma, cardiac and renal levels of proang-12 were higher than those of Ang I and Ang II. In addition, despite activation of the RAS in the systemic circulation, tissue concentrations of proang-12 were significantly reduced following treatment with losartan or imidapril. Similar reductions were also observed in the tissue concentrations of Ang II in both strains, without a reduction in Ang I. These results suggest that tissue concentrations of proang-12 and Ang II are regulated independently of the systemic RAS in WKY and SHR rats, which is consistent with the notion that proang-12 is a component of only the tissue RAS.     

Brain angiotensin in the developing spontaneously hypertensive rat

There are several factors in the manifestation of high blood pressure in spontaneously hypertensive rats (SHR) which implicate a central role for brain angiotensin II (Ang II). We have measured levels of angiotensin in the brain of SHR and rats of the Wistar-Kyoto strain (WKY). The experiments were carried out in 2-, 4-, 14- and 20-week-old rats. Areas of brain from rats were homogenized and purified with SepPak C-18 cartridges. The levels were measured by radio-immunoassay whose detection limit was 1.95 pg/tube. Significant differences were found between the different age groups and between SHR and controls. In the hypothalamus, there was a consistent elevation of brain Ang II in SHR as compared to WKY in all age groups. Cerebellum also had higher levels in SHR, especially in rats at 2 and 4 weeks of age. Brainstem levels were significantly higher in SHR only in the 14-week-old age group. Plasma levels during these time periods did not differ significantly between the strains. The results demonstrate changes in brain Ang II with development. At an early age, there are high levels of Ang II in the hypothalamus and cerebellum which do not correlate with hypertension but may be important for the development of hypertension. The higher levels of brain Ang II in SHR support the hypothesis that hypertension in SHR is related to brain Ang II activity.     

Differential Regulation of Brain Angiotensin II in Genetically Hypertensive and Normotensive Rats after Nephrectomy

To investigate the role of tissue angiotensin II (Ang II) in the maintenance of hypertension after nephrectomy in spontaneously hypertensive rats (SHR), Ang II levels were measured in various tissues of both 12-week-old SHR and normotensive control, Wistar-Kyoto rats (WKY), 48 h after nephrectomy or sham operation. Ang II was determined by radioimmunoassay coupled with high performance liquid chromatography. Nephrectomy caused a decrease of plasma renin activity and plasma Ang II concentration in both SHR and WKY. Aortic Ang II levels were significantly lowered by nephrectomy only in WKY, and not in SHR. Ang II levels in hypothalamic block, brainstem and cerebellum of SHR increased after nephrectomy, whereas those of WKY were unchanged. Intracerebroventricular administration of ceronapril, an angiotensin converting enzyme inhibitor, significantly decreased sustained high blood pressure in SHR 48 h after nephrectomy compared with vehicle administration, whereas intravenous administration had no effect. These results suggest that in spite of the important role of the renal renin-angiotensin system in maintenance of high blood pressure in SHR, control mechanisms may switch to other systems after nephrectomy, and that the increased brain Ang II levels after nephrectomy may be related to these mechanisms.     

Arterial hypertension, myocardial hypertrophy and disorders of cardiac rhythm induced by ligation of the left coronary artery in the rat

Cardiac hypertrophy and hypertension are major elements in sudden cardiac death in patients with coronary artery disease. To investigate in animals the hypothesis that left ventricular hypertrophy (LVH) and/or hypertension increase the incidence of severe ventricular arrhythmias, we have undertaken a 30 min period of coronary artery ligation in anaesthetized spontaneously hypertensive rats (SHR), normotensive (NT) Wistar Kyoto (WKY) and Wistar (W) rats. Mean systolic blood pressure (SBP) was 190 +/- 4 mmHg in SHR vs 123 +/- 5 mmHg in WKY and 116 +/- 4 mmHg in W (p less than 0.001). LVH index was 2.81 +/- 0.04 in SHR vs 196 +/- 0.03 in WKY and 1.65 +/- 0.05 in W (p less than 0.01). Incidence (IVF) and duration (DVF) of ventricular fibrillation were significantly more elevated in SHR than in NT rats. IVF was 100 p. 100 in SHR vs 36 p. 100 in WKY and 27 p. 100 in W (p less than 0.001); DVF was 61 +/- 17 s in SHR vs 6 +/- 6 s in WKY and W (p less than 0.001). In addition the calcium channel blocker nicardipine (N) has been administered orally to SHR either chronically during eight weeks (20 mg/kg-1 per os twice daily) or acutely as a single dose of 20 mg/kg. After long term treatment (LT) with N the LVH index and SBP were significantly reduced when compared to vehicle treated (VT) SHR; whereas a single administration of N (AT) only decreased SBP without affecting LVH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in cardiovascular mass, left ventricular pumping ability and aortic distensibility after calcium antagonists in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVES: To determine the effects of different dihydropyridine calcium antagonists on cardiovascular mass and function in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: The rats were treated daily for 3 weeks with nitrendipine (20 mg/kg), nifedipine (30 mg/kg), nisoldipine (6 mg/kg) or their vehicles. At the conclusion of that period left ventricular pumping ability and aortic distensibility were determined, and the aortic, cardiac and left and right ventricular masses. RESULTS: Each drug reduced arterial pressure in both rat strains; each decreased left ventricular mass in SHR but not in WKY rats. All three agents increased right ventricular mass in WKY rats; only nisoldipine did so in SHR. Each compound improved left ventricular pumping ability in WKY rats, maintaining function even when pressure was abruptly increased to pretreatment levels. In contrast, although all three calcium antagonists improved cardiac performance in SHR at the pharmacologically reduced pressures, pumping ability was not maintained when pressure was increased to pretreatment levels in nisoldipine-treated SHR. All three agents improved aortic distensibility in both strains, but only in SHR was reduced aortic mass demonstrated. CONCLUSIONS: These data not only continue to demonstrate a functional/structural dissociation associated with antihypertensive therapy, but also suggest subtle functional and structural effects that differ even within the same class of calcium antagonists.     

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.     

Cardiac thyrotropin-releasing hormone mediates left ventricular hypertrophy in spontaneously hypertensive rats

Local thyrotropin-releasing hormone (TRH) may be involved in cardiac pathophysiology, but its role in left ventricular hypertrophy (LVH) is still unknown. We studied whether local TRH is involved in LVH of spontaneously hypertensive rats (SHR) by investigating TRH expression and its long-term inhibition by interference RNA (TRH-iRNA) during LVH development at 2 stages (prehypertrophy and hypertrophy). SHR and their control rats (WKY) were compared. Cardiac hypertrophy was expressed as heart/total body weight (HW/BW) ratio. TRH content (radioimmuno assay), preproTRH, TRH receptor type I, brain natriuretic peptide (BNP), and collagen mRNA expressions (real-time polymerase chain reaction) were measured. For long-term inhibition of TRH, TRH-iRNA was injected into the left ventricle (LV) wall for 8 weeks. Hearts were processed for morphometric studies and immunohistochemical analysis using antibodies against α-smooth muscle actin and collagen type III. LV preproTRH-mRNA abundance was similar in both strains at 7 weeks of age. At the hypertrophic stage (18 weeks old), however, there was a 15-fold increase in SHR versus WKY, consistent with a significant increase in tripeptide levels and the expression of its receptor. Specific LV-TRH inhibition at the prehypertensive stage with TRH-iRNA, which decreased >50% preproTRH expression and tripeptide levels, prevented LVH development as shown by the normal HW/BW ratio observed in TRH-iRNA-treated SHR. In addition, TRH-iRNA impeded the increase in BNP and type III collagen expressions and prevented the increase in cardiomyocyte diameter evident in mismatch iRNA-treated adult SHR. These results show for the first time that the cardiac TRH system is involved in the development of LVH in SHR.     

Chronic antisense therapy for angiotensinogen on cardiac hypertrophy in spontaneously hypertensive rats

OBJECTIVE: We examined the effect of the suppression of plasma angiotensinogen (AGT) by the intravenous injection of antisense oligodeoxynucleotides (ODNs) against AGT targeted to the liver on cardiac remodeling in spontaneously hypertensive rats (SHR). The ODNs against rat AGT were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for regulating liver gene expression. METHODS: Male SHR (n = 18), and age-matched male Wistar-Kyoto rats (WKY, n = 6) were used for this study. At 10 weeks of age, the SHR were divided into three groups (each group n = 6), and the systolic blood pressure (SBP) did not significantly change among them. The control SHR and WKY groups received saline, the sense SHR group was injected with the sense ODNs complex and the antisense SHR group was injected with the antisense ODNs complex, from 10 to 20 weeks of age. ASOR-poly(L)lysine-ODNs complex was injected via the tail veins twice a week. RESULTS: At the end of the treatment, a reduction of hepatic AGT mRNA, cardiac angiotensin II type 1 receptor mRNA and the plasma AGT concentration was only observed in the antisense-injected SHR but not in the other groups of SHR and WKY. This antisense therapy did not significantly change the mRNA expression for angiotensin converting enzyme, angiotensin II type 2 receptor and AGT in the left ventricle (LV) among all three groups. Although the plasma angiotensin II (Ang II) concentration significantly decreased to the level of WKY after the antisense therapy, the SBP, LV to body weight ratio and % collagen volume fraction also showed a reduction, however, these findings were still larger than in the WKY than in either the sense-injected SHR or control SHR. CONCLUSION: The plasma AGT is considered to play a role in the development of cardiac hypertrophy in SHR, but it has not a complete effects on cardiac remodeling even if the plasma Ang II levels are inhibited because of an insufficient suppression of hypertension.     

Prolonged QT interval is associated with blood pressure rather than left ventricular mass in spontaneously hypertensive rats

QT interval is prolonged in hypertensive individuals, although the factors responsible for this increase are not completely understood. We questioned whether enhanced left ventricular mass (LVM) or increased systemic blood pressure represents the principal factor determining QT prolongation in the period of development of hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). In 12-and 20-week-old SHR (SHR12 and SHR20) and age-matched normotensive Wistar-Kyoto rats (WKY12 and WKY20), arterial systolic blood pressure (sBP) was measured using tail-cuff technique. Orthogonal Frank ECG was registered in anaesthetized animals in vivo, and bipolar ECG was measured in spontaneously beating isolated hearts in vitro. Progressive increase of sBP and LVM resulted in significant QT prolongation in SHR20 as compared to WKY12, WKY20, and also to SHR12 in vivo (WKY12: 82 +/- 9 ms, WKY20: 81 +/- 9 ms, SHR12: 88 +/- 15 and SHR20: 100 +/- 10, respectively; p < 0.05) but not in isolated hearts (WKY20: 196 +/- 39 ms and SHR20: 220 +/- 55, respectively; NS). In whole animals, QT duration was positively related to sBP (r = 0.6842; p < 0.001) but not to LVM (r = 0.1632, NS) in SHR20. The results suggest that QT prolongation in SHR developing hypertension and LVH depends on blood pressure rather than increase in LVM. In this period, myocardial hypertrophy is probably the predisposition for QT prolongation, but the significant change manifests only in the presence of elevated systemic factors.     

Early prevention of experimental left ventricular hypertrophy in experimental hypertension and angiotensin II levels]

INTRODUCTION: Angiotensin II levels can be partially inhibited during chronic administration of angiotensin converting enzyme (ACE) inhibitors, limiting from a clinical point of view its efficacy in the treatment of hypertension. There are few studies relating ACE activity directly with early prevention of left ventricular hypertrophy (LVH) in systemic hypertension during the administration of an ACE inhibitor (ACEI). AIM: To evaluate the effects of early ACE inhibition with perindopril on the development of hypertension, LVH and levels of angiotensin II (Ang II) in plasma as well as in LV in the rat Goldblatt model (Gb; 2 kidneys-1 clip), 2 weeks after surgery. RESULTS: Systolic blood pressure and relative LV mass increased by 42% and 20% respectively, in the Gb group (p < 0.001). Plasma and LV ACE activities were significantly higher in the Gb rats compared with the control rats. Plasma and LV Ang II levels also increased by 129% and 800%, respectively. Perindorpil prevented hypertension and LVH development by inhibiting plasma ACE (and also LV ACE), and also circulation Ang II in plasma and in the LV. CONCLUSIONS: In this experimental model of hypertensive LVH, there is an early activation of plasma and cardiac ACE. Early administration of an ACE inhibitor prevents the development of hypertension and LVH by inhibiting the increases of plasma and LV Ang II.     

Compensated function in hypertrophied ventricles of Wistar Kyoto and spontaneously hypertensive rats

STUDY OBJECTIVE--The aim of the study was to compare the compensatory nature of left ventricular hypertrophy in models of normal and increased peripheral resistance. DESIGN--Peak left ventricular performance was compared in normotensive Wistar Kyoto (WKY) rats, in a subset of this strain with biventricular hypertrophy associated with volume overload (WKY-CH), and in spontaneously hypertensive rats (SHR), all studied at one year of age (ie, long term hypertrophy). SUBJECTS--8 WKY-CH rats with biventricular hypertrophy were compared with 8 WKY (normal right and left ventricular weights). These groups were then compared with 9 SHR rats. All were maintained under identical conditions. MEASUREMENTS AND MAIN RESULTS--Left ventricular to body weight ratios (mg:g) were as follows: WKY-CH 2.78(SEM 0.09); SHR 2.90(0.09); WKY 2.10(0.09). Systolic blood pressures (mm Hg) were normal in WKY-CH [104(9)] and WKY [111(9)], but raised in SHR [163(8)]. Left ventricles from WKY and WKY-CH had normal histology and no fibre disorientation, fibrosis, or other morphological abnormalities. Peak cardiac index (ml.min-1.body weight-1) measured during rapid volume expansion with Tyrode's solution was higher in WKY-CH [427(33)] than in WKY [315(33)] and SHR [349(31)] (p less than 0.05). When peak stroke volume was expressed per mg left ventricular weight there were no significant differences between the groups. Peripheral resistance (mean arterial pressure divided by cardiac output) at peak cardiac output was higher in SHR [1.20(0.12)] than in either WKY-CH [0.57(0.08)] or WKY [0.74(0.08)]. CONCLUSIONS--These data show that both types of hypertrophy enhance peak left ventricular performance. In WKY-CH, which have normal peripheral resistance, the larger ventricle allows a higher peak cardiac index compared to WKY with no left ventricular hypertrophy. In SHR, the higher left ventricular mass is used to overcome an increased peripheral resistance and thereby provide a normal peak cardiac index.     

Effects of moderate diabetes on cardiac performance in spontaneously hypertensive and Wistar-Kyoto rats

To assess the effects of imposition of moderate diabetes on in vivo cardiac performance in gradually proceeding hypertension, spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) were treated with streptozotocin (40 mg/kg) or vehicle at 8 weeks of age. Four and 20 weeks later, with the rats under ether anesthesia, peak cardiac output and stroke volume were measured during volume loading and peak left ventricular developed pressure and maximum rate of rise of pressure (dP/dtmax) were determined during aortic occlusion. Additionally, passive pressure-volume relations were obtained during saline infusion in potassium-arrested hearts, and the chamber stiffness constant was derived from one exponential function. There was a mortality of 16.1% in the diabetic SHR only. While basal and stressed cardiac performance was unchanged despite the already decreased mean arterial pressure and left ventricular weight at 4 weeks, the diabetic SHR revealed significant decreases in peak cardiac pumping indexes, peak left ventricular developed pressure, and dP/dtmax, with unchanged resting cardiac function, at 20 weeks. Changes seen in the diabetic WKY were reduced left ventricular weight at 4 weeks and reduced peak left ventricular dP/dtmax at 20 weeks. The chamber stiffness was unaltered with strain or diabetes. These data show that imposition of even moderate diabetes substantially influences the stress-loaded in vivo cardiac performance in the SHR, whereas it produces only minor changes in the WKY.     

Cardiovascular mass and ventricular function after celiprolol in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: The effects of a new beta 1 adrenergic receptor blocking agent with beta 2 receptor agonistic properties on cardiovascular mass, left ventricular function, and aortic distensibility were studied in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. METHODS: 20 male SHR and 20 male WKY rats (10 treated and 10 untreated) aged 22 weeks were studied after three weeks of treatment. Cardiovascular mass was measured and left ventricular function was assessed using electromagnetic flowmetry while rapidly infusing whole blood at pharmacologically reduced mean arterial pressure and at pretreatment arterial pressure levels. Aortic distensibility was assessed by obtaining pressure-volume relationships in isolated aortic segments. RESULTS: Mean arterial pressure was reduced without changing cardiac output in SHR (p less than 0.01); it remained unchanged in WKY despite reduced cardiac output. Most noteworthy, and like no other agent studied to date, celiprolol significantly reduced both left and right ventricular as well as aortic mass in both WKY and SHR. Despite these similar mass reductions, celiprolol improved left ventricular function (p less than 0.01) and aortic distensibility (p less than 0.05) only in the SHR, a function maintained even when mean arterial pressure was increased abruptly to pretreatment levels. CONCLUSIONS: Unlike other beta receptor blockers (or any other agent studied in the SHR), celiprolol was effective in reducing mass of right and left ventricles and of aorta; decreasing mean arterial pressure through a fall in total peripheral resistance; and improving left ventricular function and aortic distensibility in the SHR. In contrast, while these structural changes were also produced in WKY, they were not associated with similar functional responses. These findings provide further support for the thesis of a structural and haemodynamic dissociation in antihypertensive therapy.     

Renal renin-angiotensin system activity in naturally reared and cross-fostered spontaneously hypertensive rats

BACKGROUND: Young (4 week) spontaneously hypertensive rats (SHR) exhibit greater renal responses to angiotensin II (Ang II) than normotensive Wistar Kyoto (WKY) rats. SHR pups cross-fostering to a WKY dam at birth (SHRX) are less sensitive to Ang II and have lower adult blood pressure. The aim of this study was to compare renal renin-angiotensin system activity in young naturally reared and cross-fostered SHR pups. METHODS: SHR and WKY rats were reared either by their natural mothers or by a foster mother of the opposite strain. At 5, 10, and 15 days of age, renal tissue renin activity and Ang II concentration were measured by radioimmunoassay. Renin-secreting cells were identified by in situ hybridization and AT(1) receptor expression was compared using Western blots. Ang II-mediated cAMP generation was measured in isolated proximal tubules. CONCLUSIONS: Tissue renin activity and numbers of renin-secreting cells did not differ, but Ang II was higher in SHRX. The AT(1) receptor expression was significantly lower in SHRX compared with SHR. Basal and Ang II-stimulated cAMP was lower in SHR tubules compared with WKY and SHRX tubules.Cross-fostering reversed the increased renal sensitivity of the SHR to Ang II. These data suggest that renal AT(1) receptor expression can be manipulated during the postnatal period and that this may affect adult blood pressure.     

Altered responsiveness of proximal tubule fluid reabsorption of peritubular angiotensin II in spontaneously hypertensive rats

Stimulation of proximal tubular fluid reabsorption by peritubular angiotensin II (Ang II) was examined by split-drop micropuncture in 5- and 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). In WKY, the maximum stimulation occurred at 10(-11) mol/l and the response did not vary with age. In 5-week-old SHR, the dose-response relationship was similar in shape and in the extent of the maximum response but was shifted one half-logarithmic step to the right, indicating decreased sensitivity to Ang II. In contrast, the dose-response relationship was shifted one half-logarithmic step to the left in 12-week-old SHR compared with WKY. Alterations in the responsiveness of the proximal tubule to Ang II in young SHR could contribute to sodium retention observed during development of hypertension in these rats.     

氯沙坦对自发性高血压大鼠左心室结构改变的实验研究

目的 :探讨氯沙坦 (Los)对自发性高血压大鼠 (SHR)左心室结构的影响。方法 :6周龄Los治疗组 (SHRlos)管饲法给予Los3 0mg kg天。治疗 17周后 ,观察 3组大鼠动脉收缩压 (SBP)、左心室 (LV)壁的厚度、左心室重量 体重 (LVW BW)以及左心室结构的变化 ;血浆放免法测肾素活性和AngⅡ含量。结果 :1 SBP :治疗结束后 ,SHRlos组血压 10 9 15± 11 3 1mmHg( 1mmHg =0 .13 3kPa) ,与对照组 (SHR)血压167 4± 13 0 1mmHg相比明显下降 (P <0 0 1)。 2 SHRlos组的LVW BW、LV壁厚度与SHR组相比明显减少 (P <0 0 1)。SHRlos心肌的超微结构与正常对照组 (WKY)相似。 3 血浆肾素活性在WKY组和SHR组之间无明显差异 (P >0 0 5 )。SHRlos组肾素活性及AngⅡ水平分别高于SHR组 (P <0 0 5 ,P <0 0 1)。结论 :Los能有效地降低SHR的血压 ,具有预防高血压LVH的作用。     

辛伐他汀对自发性高血压大鼠左心室肥厚作用及心肌转化生长因子-β1表达影响

目的观察辛伐他汀对自发性高血压大鼠左心室肥厚作用及心肌转化生长因子-β1(TGF-β1)表达的的影响。方法实验用WKY大鼠做阴性对照组,SHR大鼠分为对照组和辛伐他汀治疗组。测量大鼠尾动脉收缩压(SBP)及左心室重量指数(LVMI)。应用HE、VG染色、免疫组织化学的方法,结合计算机图像分析技术,检测心肌细胞的直径(TDM)和面积(CA)、心肌组织胶原体积比例(CVF)、血管周围胶原面积和管腔面积比例(PVCA)以及左心室心肌TGF-β1表达。结果辛伐他汀组未能有效降低血压,但可以降低左心室肥厚;SHR辛伐他汀组与SHR对照组相比TDM、CA、CVF、PVCA明显降低,TGF-β1表达下调明显(均P<0.05)。结论应用辛伐他汀治疗可逆转高血压大鼠左心室肥厚形成,TGF-β1可能与辛伐他汀逆转左心室肥厚的机制有关。