EFFECTS OF THE DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKER AMLODIPINE ON VENTRICULAR AND ATRIAL PROTEIN-SYNTHESIS IN AN AORTIC CONSTRICTION MODEL OF HYPERTENSION AND, FOLLOWING CHRONIC TREATMENT, IN THE LEFT-VENTRICLE OF SHR RATS

The dihydropyridine calcium channel blocking agent amlodipine is an ef fective anti-hypertensive agent and its use (in doses of 5 or 10 mg/da y/kg body weight) was investigated in male Wistar rats with hypertensi on induced by aortic constriction. Controls were sham-operated and pai r-fed. At the end of the study, rates of protein synthesis were measur ed with radiolabelled phenylalanine to calculate fractional rates of p rotein synthesis (k(s)), absolute rates of protein synthesis (V-s) and synthesis rates relative to RNA (k(RNA)). After 30 days of aortic con striction, weights of the left ventricle and left atrium were signific antly increased by hypertension. The weights of the right ventricle an d right atrium were relatively unaffected. Hypertension was accompanie d by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protei n contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fracti on, k(s) decreased. The right ventricle and right atrium were generall y unaffected except for a decline in mixed protein k(s). Many of these changes in hypertension were ameliorated by treatment with amlodipine , particularly at the higher dose (i.e. 10 mg/kg body weight/day) impl icating an effect on protein metabolism. In the left ventricle these i ncluded amelioration of the increases in mixed and contractile protein s, total RNA contents; mixed V-s and V-s for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hyper tension-i nduced reduction in right ventricule rates of protein synthesis. Altho ugh the preceding study emphasises the preventative aspects of amlodip ine's efficacy, an additional study was carried out in SHR rats to asc ertain the applicability for regression per se. Amlodipine (10 mg/kg/b ody weight) therapy for 30 weeks caused regression of LV mass, total p rotein, RNA and DNA contents. We conclude that amlodipine, is an effic ient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model. Copyright (C) 1997 Elsevi er Science Ireland Ltd.