CHRONIC LOW-DOSE TREATMENT WITH ENALAPRIL-INDUCED CARDIAC REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY

Numerous studies suggest that the renin angiotensin system (RAS) is in volved in the development of cardiac hypertrophy. In the present study we produced cardiac hypertrophy in rats subjected to abdominal aortic banding and also induced cardiac regression by the administration of an angiotensin converting enzyme (ACE) inhibitor, enalapril, at 3, 10 and 30 mg/kg/day. Each drug was administered to the rats for 6 weeks f rom 6 weeks after aortic banding. The left ventricular weight signific antly decreased at 10 and 30 mg/kg/day of enalapril as well as the sys tolic blood pressure. Using the reverse transcriptase polymerase chain reaction, the increased levels of ACE and AT1 mRNA were significantly inhibited in the aortic banding rats treated with the above concentra tions of enalapril. The ACE activity in both the plasma and heart tiss ue preparations was significantly inhibited by enalapril. Similar obse rvations were also seen after the administration of angiotensin type 1 receptor blockade, E-4177, into the aortic banding rats. The treatmen t with enalapril at 3 mg/kg/day did not reduce the left ventricular we ight or the systolic blood pressure in the aortic banding rats. Howeve r, this low-dose treatment did significantly decrease the left ventric le to body weight ratio in the aortic banding rats without a reduction of the systolic blood pressure. Therefore, using the low-dose enalapr il, the ACE activity in plasma was in part inhibited and the levels of ACE mRNA also decreased in the heart tissue of aortic banding rats, w hile the level of AT1 mRNA showed no such decrease. These results thus indicate that chronic ACE inhibitor at low doses has a beneficial eff ect on the regression in the pressure-induced cardiac hypertrophy. It is thus assumed that this effect may also contribute to the presence o f an alternate pathway for the conversion of angiotensin I to angioten sin II which might also act as a possible mechanism for cardiac regres sion.