アンジオテンシンI変換酵素阻害薬(SQ14225;カプトプリル)の降圧機序に関する研究

概要

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In order to clarify the mechanism of the hypotensive action of captopril, the acute and chronic effects of this drug on the kallikrein-kinin and renin-angiotensin systems were investigated in 10 and 12 in-patients with essential hypertension, respectively. In the study of the acute effects of captopril, a dose of 50 mg of this drug was administered once orally in the early morning after a night of fasting. For the chronic effect, 75 mg of this drug was administered three times a day for 14 days. In observations of the acute effects of captopril, blood pressure decreased significantly at 30 minutes and maximally at 60-180 minutes after the administration, while no change in the heart rate was found during this same period. Significant increases in plasma kinin level and plasma renin activity (PRA), and decreases in plasma angiotensin II level were observed. A significant increase was also found in urinary kinin excretion, but not in urinary kallikrein excretion. Moreover, the changes in blood pressure negatively correlated with the basal PRA, basal plasma angiotensin II and the changes in plasma kinin levels, and positively with the changes in plasma angiotensin II levels. In the study of the chronic effects of captopril, the changes in plasma kinin levels, PRA, plasma angiotensin II levels, blood pressure and heart rate were essentially similar to those observed in the acute study. Significant correlations of the changes in blood pressure were negatively found with basal PRA, basal plasma angiotensin II levels and the changes in plasma kinin levels, and positively with the changes in plasma angiotensin II levels. These data suggest that the hypotensive effects of captopril might be caused, in part, by a decreased activity of the renin-angiotensin system through a decrease of angiotensin II production, and an increased activity of the kallikrein-kinin system through an inhibition of kinin destruction. In addition, significant increases in urine volume and urinary sodium excretion occurred following the administration of captopril for 14 days, and both increases correlated negatively with the changes in blood pressure. Moreover, the changes in urinary sodium excretion correlated positively with the changes of plasma kinin levels and tended to correlate negatively with the changes of plasma angiotensin II. Furthermore, an augmented urinary excretion of kinin had been observed in the study of the acute effects of captopril. Therefore, it was assumed that the increases in urine volume and urinary sodium excretion may be caused by the augmented blood kinin levels, and reduced plasma angiotensin II levels through the increase of renal blood flow. It should be considered that these increases in urine volume and urinary sodium excretion may also partly contribute to the hypotensive effects of captopril. From these results, it was concluded that the hypotensive effect of captopril might be caused to some degree by a decrease in plasma angiotensin II levels and an increase in plasma kinin levels, and by an augmentation of urine volume and urinary sodium excretion during long-term administraton.
札幌医科大学の論文
1988-08-01

アンジオテンシンI変換酵素阻害薬(SQ14225;カプトプリル)の降圧機序に関する研究

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概要

札幌医科大学 | 論文

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