Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats.

The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.     

ABNORMALITY OF THE GLOMERULAR ANGIOTENSIN II RECEPTOR IN EXPERIMENTAL DIABETIC NEPHROPATHY

1. The combined effect of diabetes and hypertension on the plasma angiotensin II (AII)/glomerular AII receptor (AII-R) relationship in streptozotocin-induced diabetes was investigated as well as the effect of glycaemic control on this relationship. 2. Diabetes was induced in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with streptozotocin 60 mg/kg and blood sugars maintained between 18–21 mmol/L (uncontrolled diabetes) and 4–8 mmol/L (controlled diabetes). Rats were killed on days 1 and 7. Angiotensin II receptor was estimated by saturation analysis and plasma AII by radio-immunoassay. 3. Angiotensin II receptors were significantly higher in non-diabetic SHR than WKY rats (708 ± 62 and 388 ± 36 fmol/mg protein, respectively, P = 0.0008). Plasma AII were comparable in both groups (47 ± 2.7, 38 ± 3.5 pg/mL, respectively) and a significant inverse relationship between AII/AII-R was observed (WKY P = 0.02 and SHR P = 0.004). 4. On day 7, plasma AII and AII-R levels in diabetic groups were comparable with those of their non-diabetic controls. Diabetic WKY rats maintained an inverse correlation between AII and AII-R (controlled P= 0.04 and uncontrolled P= 0.015), but this did not occur in the SHR. 5. Absence of receptor response to varying ligand concentrations in the diabetic SHR may contribute to the development of nephropathy. Glycaemic control does not appear to reverse this abnormality in the SHR, so that co-existent hypertension may have a more direct influence on renal function.     

AUGMENTATION OF ANGIOTENSIN II RELEASE FROM ISOLATED MESENTERIC ARTERIES OF WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING NEPHRECTOMY

1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.     

Hypotensive effects of dihydropyridine derivatives

Effects of six dihydropyridine derivatives (nifedipine, nisoldipine, nitrendipine, nicardipine, nimodipine and niludipine) and hydralazine on blood pressure and heart rate in spontaneously hypertensive rats (SHR) were studied in comparison with those in normotensive rats (NR). Nisoldipine, nitrendipine and nicardipine showed stronger hypotensive effect in SHR than in NR. All the dihydropyridine derivatives--especially nifedipine, nitrendipine and niludipine--lowered blood pressure of SHR at doses smaller than those producing positive chronotropic effect. Hydralazine caused hypotensive effect in the same extent both in SHR and in NR and, moreover, it brought about tachycardia at doses smaller than those lowering blood pressure.     

Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: effects on nociceptive behavior and cardiovascular regulation

Effects of s.c. capsaicin pretreatment on nociception, mean systemic arterial blood pressure, and dose-response curves for depressor effects of substance P (SP) and pressor effects of angiotension II (AII) and norepinephrine (NE) were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Capsaicin pretreatment significantly elevated hot plate and tail flick latencies in SHR subjects but was without effect in WKY rats. Capsaicin pretreatment significantly reduced mean systemic arterial blood pressure in rats of both strains. Both vehicle- and capsaicin-treated WKY subjects exhibited greater depressor responses than did subjects of the corresponding SHR groups after i.v. SP administration. Vehicle-treated SHR subjects exhibited greater pressor responses to both AII and NE than did rats of the vehicle-treated WKY group. Capsaicin treatment decreased the sensitivity of WKY rats to the pressor effects of both AII and NE. Strain differences involving nociception, cardiovascular regulation, and responses to capsaicin may underly the results reported.     

Atrial natriuretic factor and volume expansion-induced natriuresis in the spontaneously hypertensive rat.

The implication of atrial natriuretic factor (ANF) during acute volume expansion in the spontaneously hypertensive rat (SHR) was evaluated. The effect of short-term afterload relief was also investigated. Fourteen- to 15-week-old SHR and Wistar-Kyoto (WKY) rats were treated with hydralazine for 5 days. The systolic blood pressure (BP) of SHR decreased to normotensive levels but cardiac hypertrophy was not reduced. Isotonic, iso-oncotic volume expansion (equivalent to 10% of total blood volume) was performed 3 times at 15-min intervals on conscious animals. The effect of volume expansion on central venous pressure was identical among the groups. Changes in left ventricular end-diastolic pressure (LVEDP) induced by volume expansion were greater in SHR than in WKY rats and were not affected by treatment. The increases in plasma N-terminal ANF (ANF-(1-98)) concentrations were larger in both treated and untreated SHR verses WKY rats. Despite enhanced ANF release in SHR, the overall magnitude of the diuretic and natriuretic responses to volume expansion was similar in all groups. The natriuretic response was strongly correlated with plasma ANF in WKY rats, this relationship was weak in control SHR, and restored by treatment. It is suggested that ANF release is not impaired in SHR at a 10% volume load; however, there seems to be a lower renal responsiveness to ANF in SHR.     

HAEMODYNAMIC RESPONSES TO RAT ADRENOMEDULLIN IN ANAESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive peptide, were examined in anaesthetized 16–18 week old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). 2. An intravenous injection of rat AM dose-dependently reduced the mean blood pressure (MBP) with a concomitant fall in total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in both strains of rats. Per cent changes in MBP, TPRI and CI were not different between SHR and WKY. 3. The plasma half-life of rat AM in SHR was similar to that in WKY when it was administered at the dose of 1.0 nmol/kg. 4. These findings indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The haemodynamic responsiveness to exogenous AM and its pharmaeokinetics in SHR were comparable with those in WKY.     

Antihypertensive effect of ragaglitazar: a novel PPARalpha and gamma dual activator.

Ragaglitazar is a novel and potent dual peroxisome proliferators activated receptor (PPAR) alpha and gamma activator. The aim of this study is to investigate the effect of ragaglitazar on blood pressure and endothelial function in insulin resistant animal model and non-insulin resistant hypertensive models. The effects ragaglitazar were tested in Zucker fa/fa, spontaneously hypertensive rats (SHR), 2 kidney 1clip rat (2K1C) and Wistar Kyoto rats (WKY). Pioglitazone was taken as a comparative standard. Ragaglitazar showed significant reduction (P<0.001) of systolic blood pressure (SBP) in insulin resistant fa/fa rats, with concomitant reduction in plasma triglycerides (TG) and insulin levels while pioglitazone (10 mg kg(-1)) showed significant (P<0.05) but comparatively less reduction. Ragaglitazar in contrast to pioglitazone showed significant reduction (P<0.05) of SBP in SHR, 2K1C while the same dose did not have any effect on normotensive WKY. Ragaglitazar also showed significant improvement in acetylcholine-induced relaxation in isolated aorta of Zucker fa/fa, SHR, 2K1C and also potentiated the insulin-induced vasorelaxation in Zucker fa/fa rats. These findings summarize that ragaglitazar shows significant reduction of BP and improvement in endothelial function not only in insulin resistant but also in non-insulin resistant hypertensive models where standard thiazolidinediones are ineffective. These data indicates that dual PPARalpha and gamma activator ragaglitazar can be beneficial for the treatment of hypertension and vascular disease commonly associated with type 2 diabetes.     

Down-regulation of the GABA-ergic system in selected brain areas of spontaneously hypertensive rats (SHR)

The relevance of GABA-ergic system in hypertensive state has been studied. GABA content, GAD activity and GABA-A receptor binding in various brain areas in age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY) was compared. Out of 9 brain areas studied the GABA content was significantly lower in the substantia nigra, hypothalamus, hypothalamus posterior and hippocampus of SHR rats. GAD activity was lowered in the hypothalamus and hippocampus of young SHR and adult SHR rats (4, 8, 14 weeks old). Scatchard analysis of the binding isotherms indicated a lower Bmax of the binding sites in the hypothalamus and hippocampus of 8 and 14 weeks old SHR rats. These results suggest that activity of GABA-ergic system differs substantially in SHR and WKY rats brain. Furthermore, these differences appear already in young prehypertensive SHR rats as well as in the early stages of hypertension.     

Blood pressure and hypothalamic NA-GABA interaction in spontaneously hypertensive rats (SHR): effect of administration DSP-4

The effect of DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] on the content of catecholamines (NA and DA) and gamma-aminobutyric acid (GABA) in the hypothalamus and on the blood pressure were studied in rats. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were injected with DSP-4 (50 mg/kg i.p. twice) and tested for 15 days thereafter. Fifteen days after DSP-4 lesioning, a significant reduction of NA levels without changes in DA and GABA concentration in the hypothalamus of both strains was found. However the blood pressure appeared unaffected by the DSP-4 pretreatment in WKY and SHR rats. In line with previous data the amounts of catecholamines and GABA in the hypothalamus were significantly lower in SHR control animals than in WKY control rats. The results suggest that NA/GABA interaction in the hypothalamus do not play an important role in blood pressure regulation. It may be further supposed that the local NA transmission does not play an important role in the phenomenon discussed. Moreover, a contribution of hypothalamic GABA and DA to the control of blood pressure is confirmed.     

Hypotensive effects of sarthran in normotensive and spontaneously hypertensive rat strains.

The specific angiotensin receptor antagonist [Sar1, Thr8]AII (sarthran) was intracerebroventricularly (ICV) infused in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive controls. The results extend earlier findings by determining that: 1) the hypotensive effect of ICV-infused sarthran could be enhanced in anesthetized as compared with alert animals; 2) SHRs revealed a greater hypotensive response as compared with WKY rats; and 3) no sarthran-induced agonistic effects were observed in contrast with previous results using alert SHRs. These findings support the use of sarthran as a potent angiotensin receptor antagonist to investigate the role of the brain angiotensin system in the control of normal and dysfunctional blood pressure.     

Hydralazine reduces leukocyte migration through different mechanisms in spontaneously hypertensive and normotensive rats

In addition to reducing blood pressure, hydralazine can reduce the production of inflammatory cytokines and reduce the expression of leukocyte adhesion molecules. Differences in leukocyte behavior and leukocyte adhesion molecule expression in spontaneously hypertensive rats (SHR) compared to normotensive rats have been reported. However, whether hydralazine can reduce leukocyte migration in vivo in hypertension and in normotension remains unknown. To address this question, male SHR and Wistar rats were treated for 15 days with hydralazine at a dose of ~3.5 mg/kg or ~14 mg/kg in their drinking water. The numbers of rollers and adherent and migrated cells were determined by direct vital microscopy, and blood pressure was assessed by tail plethysmography. In addition, following treatment with the higher dose, immunohistochemistry was used to measure the expression of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cells, while flow cytometry was used to evaluate the expression of leukocyte CD18 and L-selectin. Hydralazine reduced leukocyte adherence and migration in SHR either at the higher, that reduced blood pressure levels, or lower dose, which did not reduce it. Reduced ICAM-1 expression might be involved in the reduced migration observed in SHR. In Wistar rats, only at the higher dose hydralazine reduced blood pressure levels and leukocyte migration. Reduced P-selectin expression might be involved. We therefore conclude that hydralazine reduces leukocyte migration by different mechanisms in SHR and Wistar rats, specifically by reducing ICAM-1 expression in the former and P-selectin expression in the latter.     

氯沙坦对自发性高血压大鼠细胞外信号调节激酶活性和B型利钠肽表达的影响

目的　探讨氯沙坦治疗高血压心肌肥厚的作用机制。方法　选择同周龄WistarKyoto(WKY)大鼠作正常对照,将2 1只14周龄雄性自发性高血压大鼠(SHR)随机分成3组:模型组、肼屈嗪组(10mg·kg- 1·d- 1)和氯沙坦组(10mg·kg- 1·d- 1)。用West ern印迹方法检测大鼠心肌总细胞外信号调节激酶(t ERK)、磷酸化ERK(p ERK)及有丝分裂素激活蛋白激酶磷酸酶 1(MKP 1)水平;用RT PCR法半定量测定大鼠心肌中B型利钠肽(BNP)mRNA的含量;酶联免疫吸附法检测大鼠血浆BNP水平。结果喂药10周后,氯沙坦组和肼屈嗪组血压相似,均显著低于模型组(n =7,P <0 .0 1)。氯沙坦组心肌肥厚指数显著低于肼屈嗪组和模型组(n =7,P <0 .0 1) ,与WKY组无差异(n =7,P >0 .0 5 ) ;肼屈嗪组和模型组心肌肥厚指数无差异(n =7,P >0 .0 5 )。4组大鼠t ERK水平无显著性差异(n =7,P >0 .0 5 ) ;氯沙坦组心肌p ERK ,p ERK/t ERK及MKP 1水平均显著低于SHR肼屈嗪组和SHR模型组(n =7,P <0 .0 5 ) ,与WKY组无差异(n =7,P >0 .0 5 )。肼屈嗪组和模型组心肌p ERK ,p ERK/t ERK及MKP 1水平无差异(n =7,P >0 .0 5 )。氯沙坦组大鼠心肌BNPmRNA和血浆BNP水平显著低于SHR肼屈嗪组和模型组(n =7,P <0 .0 5 ) ,与WKY组无差异(n =7,P >0 .0 5 ) ;肼屈嗪组和SHR模型组大鼠     

吴茱萸次碱对高血压大鼠血压的影响及作用机制

目的观察吴茱萸次碱对高血压模型大鼠血压的影响,并初步探讨其作用机制。方法分别采用自发性高血压大鼠(SHR)及两肾一夹(2K1C)高血压大鼠模型,设正常对照组、模型组、卡托普利阳性组及吴茱萸次碱低、中、高剂量组(10,20,40 mg/kg),每日灌胃给药1次,给药4周,每周测定1次血压,末次给药后,腹主动脉取血,分别测定血浆血栓素(TXB2)、6-酮-前列腺-F1α(6-Keto-PGF1α)、肾素活性(PRA)、心房钠肽(ANP)水平。结果在两个模型中吴茱萸次碱均有较好的降压作用,并能使SHR大鼠血浆TXB2水平降低,6-Keto-PGF1α水平升高;使2K1C大鼠血浆PRA、ANP水平升高。结论吴茱萸次碱能明显降低SHR及2K1C大鼠血压,其降压效果可能通过调节PGI2和TXA2水平,改善血管内皮功能及增加舒血管物质ANP水平实现的。     

高血压前期药物干预对卒中易感型自发性高血压大鼠的影响

目的比较氯沙坦和氨氯地平的高血压前期干预对卒中易感型自发性高血压大鼠（SHRSP）血压和循环及脑组织肾素-血管紧张素-醛固酮系统的影响。方法 SHRSP组分为氯沙坦组、氨氯地平组。Wista大鼠（WKY）作为对照组。6周后,测量收缩压、血浆和脑组织中的血管紧张素（AngⅡ）和醛固酮（Aldo）含量、脑组织血管紧张素Ⅰ型受体（AT1R）和Ⅱ型受体（AT2R）蛋白表达。结果 10周龄时,SHRSP组比WKY组的收缩压明显降低（P〈0.05）;氯沙坦提高血浆AngⅡ水平,降低血浆及脑组织Aldo水平（P〈0.05）。同时,氯沙坦和氨氯地平可降低大脑皮层AT1R蛋白表达（P〈0.05）。结论氯沙坦和氨氯地平干预均可有效延缓血压进展;氯沙坦对SHRSP循环及脑组织肾素血管紧张素醛固酮系统均有抑制作用。     

Effects of dihydropyridine-type Ca2+ antagonists on the renal arterial tree in spontaneously hypertensive rats.

The effects of hypertension and of treatment with dihydropyridine-type Ca2+ antagonists and the vasodilator hydralazine on renal arterial tree were investigated in spontaneously hypertensive rats (SHR) with quantitative microanatomical techniques. Pharmacological treatment decreased to a similar extent systolic blood pressure values in SHR. Increased thickness of the tunica media of intrarenal arteries accompanied and luminal narrowing were observed in control SHR. Lercanidipine, manidipine, and nicardipine significantly countered wall thickening and luminal narrowing. Hydralazine countered luminal narrowing only. Dihydropyridines exerted renal vasocilatory activity primarily on resistance arteries, being lercanidipine the only compound active on small sized arteries.     

Effect of clonidine on renal sodium handling in spontaneously hypertensive rats

Up-regulation of kidney α2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 μg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion.     

KYNURENIC ACID, AN ENDOGENOUS GLUTAMATE ANTAGONIST, IN SHR AND WKY RATS: POSSIBLE ROLE IN CENTRAL BLOOD PRESSURE REGULATION

1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar-Kyoto rats: WKY). 2. Of the brain regions examined the highest kynurenine aminotransferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activity. 3. All samples from SHR showed greatly reduced kynurenine aminotransferase activity compared to WKY. These reductions were most pronounced in the medulla and spinal cord, approximately 45–55%, and lowest in the cerebellum and olfactory bulbs, approximately 25–30%. 4. The kynurenic acid content of the rostral and caudal medulla as well as the spinal cord was also significantly lower in SHR. 5. These results suggest that there may be a deficiency in the kynurenic acid content and kynurenine aminotransferase activity in the SHR. 6. Given the accumulating evidence of the importance of medullary glutamatergic pathways in the control of blood pressure, as well as the higher sensitivity of cardiovascular neurons of SHR to applied glutamate, it seems possible that endogenous kynurenic acid in the brain may play a role in the control of blood pressure and the pathogenesis of experimental hypertension in the SHR.     

Alterations of renal vasopressin V1A and V2 receptors in spontaneously hypertensive rats

To elucidate the role of arginine vasopressin (AVP) in a hypertensive state, the characteristics of renal cortex V(1A) and medulla V(2) receptors in young spontaneously hypertensive rats (SHR) during the developmental phase of hypertension were compared with those of age-matched Wistar-Kyoto (WKY) rats using the radioligand receptor assay technique. The systolic blood pressure of 8-week-old SHR was statistically significantly higher than that of WKY rats (142 +/- 1 vs. 125 +/- 2 mm Hg). The plasma AVP levels were also significantly higher in SHR than in WKY rats (3.20 +/- 0.41 vs. 1.96 +/- 0.34 pg/ml). In SHR, the maximum capacity of (3)H-d(CH(2))(5)Tyr(Me)AVP binding to cortical V(1A) receptors (B(max)) was statistically significantly higher than that of WKY rats (39.7 +/- 2.7 vs. 22.4 +/- 0.9 fmol/mg protein). Furthermore, the B(max) values of (3)H-AVP binding to medullary V(2) receptors in SHR were also significantly higher than in WKY rats (40.2 +/- 1.9 vs. 28.3 +/- 1.3 fmol/mg protein). However, the apparent dissociation constant (K(d)) values of renal cortex V(1A) and medulla V(2) receptors in SHR and WKY rats were not significantly different. These results indicate that increased amounts of renal cortex V(1A) and medulla V(2) receptors in SHR play an important role in the pathophysiology of hypertension.     

高血压性左心室肥厚与心肌原癌基因c-fos表达

采用自发性高血压大鼠(SHR)和两肾一夹型(2K1C)肾血管性高血压大鼠模型，研究细胞核内原癌基因c-fos在高血压性左心室肥厚(LVH)发生，发展过程中的作用. 结果表明：SHR在8-10周龄时已有明显的高血压和LVH，其收缩压(SBP)与左室重/体重比(LVW/BW)均显著高于同龄的WKY大鼠. 20-22周龄与40-42周龄时，SHR的SBP，LVW/BW及左心室c-fos基因表达水平均明显高于同龄对照组WKY大鼠. 2K1C大鼠左肾动脉缩窄1周后发生明显的LVH，同时伴左心室c fos基因的高表达，至术后3和10周仍保持较高水平. 钙拮抗剂尼群地平(10 mg·kg^-1 ig，每日2次，连续10周)或血管紧张素AT₁受体阻断剂洛沙坦(30 mg·kg^-1·d^-1 ig，连续10周)治疗均可逆转2K1C大鼠SBP的增高和LVH的发生与发展，同时左心室c-fos基因表达水平降低. 结果提示心肌原癌基因c-fos的高表达参与高血压性LVH的发生，发展过程.