Comparative effects of α-methyldopa, propranolol and hydralazine therapy on cardiac adenylate cyclase activity in normal and spontaneously hypertensive rats

Normotensive (WKY) and spontaneously hypertensive (SHR) male rats were treated orally, one week after weaning for 9 weeks, with α-methyldopa (100 mg/kg per day), propranolol (30 mg/kg per day) or hydralazine (10 mg/kg per day). Untreated WKY and SHR rats served as controls. The development of hypertension in SHR rats was attenuated by treatment but none of the drugs was able to restore the impairment in isoproterenol, secretin and glucagon responsiveness of cardiac adenylate cyclase activity which is characteristic of these animals. In heart membranes from both WKY and SHR rats, α-methydopa treatment increased the number of β-adrenoceptors by 20–32% and the maximal response of adenylate cyclase activity to isoproterenol and glucagon by 20–34%. By contrast, the β-blocker propranolol was ineffective on these parameters. The results obtained are consistent with the hypothesis that the change in adenylate cyclase seen in SHR rats is generic in origin and is not a consequence of hypertension.