Effect of pravastatin on development of left ventricular hypertrophy in spontaneously hypertensive rats

Abstract

Endothelin (ET)-1 has been implicated in the development of cardiac hypertrophy. We investigated the effect of pravastatin on development of ventricular hypertrophy in spontaneously hypertensive rats (SHR) and whether the attenuated hypertrophic effect was via reduced ET-1 expression. Normolipidemic SHR were treated with one of the following therapies for 8 wk: vehicle, the nonselective ET receptor antagonists bosentan, pravastatin, mevalonate, hydralazine, or combination of pravastatin + mevalonate from the age of 8 wk at the very early stage of cardiac hypertrophy. Treatment with bosentan and pravastatin significantly decreased left ventricular mass index for body weight and cardiomyocyte sizes isolated by enzymatic dissociation. The myocardial ET-1 levels and preproET-1 mRNA assessed using real-time quantitative RT-PCR were significantly higher (both P < 0.001) in the SHR compared with Wistar-Kyoto rats. The increased tissue ET-1 levels can be inhibited after pravastatin administration. Immunohistochemical analysis confirmed the changes of ET-1. Left ventricular mass index for body weight correlated positively with tissue ET-1 levels (P = 0.0004). A dissociation between the effects of blood pressure and cardiac structure was noted, because pravastatin and hydralazine reduced arterial pressure similarly. Pravastatin-induced effects were reversed by the addition of mevalonate. In conclusion, these results suggest a crucial role of cardiac endothelin system in the early development of ventricular hypertrophy in the SHR. Pravastatin is endowed with cardiac antihypertropic properties that are independent of its hemodynamic and hypolipidemic effects and appear to be related to their capacity to decrease cardiac ET-1 levels, which is linked to mevalonate metabolism.

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

“…Moreover, in experimental hypertension, treatment with a selective ETA-receptor antagonist attenuated left ventricular hypertrophy, prevented vascular hypertrophy and ameliorated endothelial dysfunction. 29 In our study, intravenous infusion of DRPs significantly increased blood shear stress, which may suppress ET-1 expression in left ventricular and thoracic aorta and left ventricular hypertrophy and aortic remodeling (Figures 3-5).…”

Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failure model rats

“…However, our data are partially inconsistent with previous studies. In previous studies reporting the attenuation of cardiac fibrosis by preventing hypertension and left ventricular hypertrophy by statin therapy, the statin treatment was started at an earlier phase of salt loading [13,[28][29]. In our study, statin was administrated after the establishment of hypertension and left ventricular hypertrophy.…”

Anti-inflammatory effects of atorvastatin improve left ventricular function in experimental diabetic cardiomyopathy

“…Whereas the cardioprotective effects of statins, independent of their hypolipidaemic effects, have already been demonstrated in several normocholesterolaemic models [14,15,38], this is the first animal study demonstrating the pleiotropic effects of statins in a model characterised by increased LDL-cholesterol levels.…”

“…Many of these pleiotropic effects are mediated by antagonism of isoprenoid-mediated activation of small GTPbinding proteins, such as RHO family members, including ras-related C3 botulinum toxin substrate (RAC1) and ras homologue gene family, member A (RHOA) [11], activation of the latter being associated with decreased endothelial nitric oxide synthase (eNOS) expression and activity [12,13]. The cardioprotective effects of statins, independent of their hypolipidaemic effects, have already been demonstrated in normocholesterolaemic animal models of hypertrophy [14] and myocardial infarction [15]. However, their pleiotropic effects have not been investigated before in an animal model associated with increased LDL-cholesterol.…”