アンジオテンシンI変換酵素抑制剤captopril慢性投与による血圧ならびにレニン・アンジオテンシン・アルドステロン系の変化に関する実験的研究

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概要

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• The chronic effects of the oral administration of an angiotensin converting enzyme inhibitor (captopril, 63-80 μg/kg/day) on blood pressure and the renin-angiotensin-aldosterone system were studied in normotensive male Wistar rats. The 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 2, 9, 19, 29 and 58 days after the administration of the agent. Blood pressure was determined in unanesthetized rats, and blood samples were obtained by de-capitation. Furthermore, blood pressure responses to bolus injections of angiotensin II (AII, 80 ng/kg), angiotensin I (AI, 80 ng/kg) and bradykinin (BK, 10 μg/kg) were examined in unanesthetized rats which had been given the agent for 20 days. The BP of the rats which had been given captopril for 9 days or more was significantly lower than in the control rats. The reduction in heart weight in the captopril rats reached a statistically significant level 58 days after the administration of the agent. The PRA and the PRC markedly increased, and the PRS and the PAC both decreased in the captopril rats. The RRC which was reduced after 2 days of captopril administration markedly increased thereafter. In the captopril rats, significant negative correlations were observed between PRC and PRS (r=- 0.43, p<0.01), and between BP and PRC (r=-0.60, p<0.001). The PRC significantly correlated with the RRC in the control rats (r=0.44, p<0.01) while such a relationship did not exist in the captopril rats. Although the pressor responses to All were similar in the captopril and the control rats, the responses to AI were reduced to 50% of the responses to All in the captopril rats. The blood pressure reduction in response to BK in the captopril rats was 2.3 times as great as that in the control rats. Thus, it is suggested that the increases in PRA, PRC and RRC in the captopril rats may be related to both the blood pressure reduction and interruption of the negative feedback inhibition of renin synthesis and release by AII, and that the decrease in PRS in the captopril rats is due to the increased consumption and probably to the decreased rate of substrate production in the liver which is secondary to the decrease in plasma AII. The lack of a significant positive correlation between PRC and RRC in the captopril rats seems to demonstrate that captopril may modify the relationship between them. The results also show that the chronic administration of captopril lowers blood pressure in normotensive animals. The blood pressure reduction by captopril may be related to the decreased kininase activity which is suggested by the enhanced depressor responses to BK, as well as the lowered plasma level of AII.

• 一般社団法人 日本内分泌学会の論文

著者

• 後藤 淳郎

  東京大学医学部第二内科

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• アンジオテンシンI変換酵素抑制剤captopril慢性投与による血圧ならびにレニン・アンジオテンシン・アルドステロン系の変化に関する実験的研究

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