Studies on renin-angiotensin system. I. Angiotensinase activities in hepatic disorders

Abstract

Many reports have been made of the spontaneous improvement of hypertension after the development of liver diseases ; however, the mechanism of this fact remains obscure. It is imaginated that an angiotensin destroying substance, so-called angiotensinase, is responsible somehow for the mechanism of the reduction of high blood pressure observed in the patients with liver diseases since angiotensinase probably helps regulate the plasma and tissue concentrations of angiotensin and hence its potent physiologic effects. From this standpoint, the experiments were divised to investigate first the change of plasma angiotensinase activity in patients with hepatobiliary diseases and second that in rats with hepatic damages induced by carbon tetrachloride or ligation of the common bile duct. Material and Methods. 1) Clinical Observations. Observations were made on 74 patients with hepatobiliary diseases and 50 patients with other miscellaneous diseases. Angiotensinase activity was determined by a method based on the degradation of pressor activity of synthetic valine-5-angiotensin II-aspartic-β-amide by fresh heparinized plasma from fasting subjects. Blood pressure was recorded by means of a mercury manometer connected with the carotid artery of a rat weighing 150-200g anesthetized with pentobarbital sodium. 2) Experimental Observations. Observations were made on 21 control and 21 experimental male Wistar rats weighing 200-250g maintained on Oriental MF rat chow . Hepatic injuries were induced as follows ; 1. acute carbon tetrachloride intoxication, twenty-four hours after carbon tetrachloride injection (0.5 ml of 20 % carbon tetrachloride olive oil solution per 100g body weight subcutaneously) 2. chronic carbon tetrachloride intoxication, after carbon tetrachloride injections once a week for 6 weeks. 3. obstructive jaundice, one week after ligation of the common bile duct. Livers of experimental and control animals were examined microscopically at the end of the experiment. Angiotensinase activities of plasma and of liver homogenates were determined by the method mentioned previously.