ANGIOTENSIN Ⅱ ANTAGONIST, TCV-116, PREVENTS CARDIAC HYPERTROPHY AND FIBROSIS IN SPONTANEOUSLY HYPERTENSIVE RAT BY SUPPRESSING SYMPATHETIC NERVE ACTIVITY

Abstract

I investigated effects of AⅡ receptor antagosist, (TCV-116) on suppression of cardiac hypertrophy and fibrosis via sympathetic nerve activity in the spontaneously hypertensive rat (SHR). Method : SHR was administered orally AⅡ receptor antagonist, (TCV-116), angiotensin converting enzyme inhibitor, (cilazapril), β-receptor blocker (metoprolol), and arterial vasodilator, (hydralazine) for 16 or 24 weeks. Pathophysiological study was performed to evaluate cardiac hypertrophy and fibrosis. Plasma concentration of catecholamines and density of β-adrenoceptors in cardiac myocyte were evaluated to determine sympathetic nervous system activity. Result : AⅡ antagonist and ACE inhibitor prevented cardiac hypertrophy and development of myocar- dial fibrosis to a greater extent than other agents tested. While β-adrenergic blocker also suppressed myocardial hypertrophy and fibrosis, its effects were weaker than those of AⅡ antagonist and ACE inhibitor. Bmax of myocardial adrenergic receptor was significantly higher in the groups administered with AⅡ antagonist, ACE inhibitor, and β-adrenergic blocker as compared with hydralazine treated and untreated groups. Bmax of myocardial adrenergic receptor and plasma concentration of catecholamine level did not differ among groups receiving AⅡ antagonist, ACE inhibitors and β-adrenergic blocker. Conclusion : A Ⅱ antagonist and ACE inhibitor suppressed activity of renin-angiotesin system (RAS) and that of sympathetic nervous system, and AⅡ antagonist and ACE inhibitor may be more effective than β-adrenergic blocker or hydralazine in preventing cardiac hypertrophy and fibrosis in SHR.