抄録
The chronic effects of oral administration of an angiotensin converting enzyme inhibitor (captopril, 63-80mg/Kg/day) on blood pressure and the renin-angiotensin-aldosterone system were-studied in normotensive male Wistar rats. Blood pressure (BP), plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin substrate concentration (PRS), plasma aldosterone concentration (PAC) and renal renin content (RRC) were measured after 2, 9, 19, 29 and 58 days of captopril administration. BP was determined in awake rats and blood samples were obtained by decapitation. In addition, BP responses to bolus injections of angiotensin I (AI, 80ng/Kg), angiotensin II (AII, 80ng/Kg) and bradykinin (BK, 10μg/Kg) were examined in conscious rats which had received captopril for 20 days. The BP of the rats which had been given captopril for 9 days or longer was significantly lower than that of the control rats. PRA and PRC were markedly increased, and both PRS and PAC were decreased in the captopriltreated rats. RRC, which was reduced after 2 days of captopril administration, was substantially increased thereafter. Although the pressor responses to AII were similar in the captopril treated and the control rats, the responses to AI were reduced to 50% of those to AII in the former. The depressor responses to BK in the captopril-treated rats were 2.3 times as large as those in the control rats. Our results show that long-term use of captopril lowers BP in normotensive rats on a normal sodium intake. They also suggest that the rises in PRA, PRC and RRC in the captopril-treated rats may be related to the effects of both the BP reduction and interruption of the negative feedback mechanism of All on renin release and synthesis, and that the decline in PRS is due to its increased consumption and probably also to the decreased rate of hepatic substrate synthesis induced by the fall in plasma AII.
