変換酵素抑制薬カプトプリル長期投与による降圧効果ならびに降圧機作に関する内分泌学的研究

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SQ 14,225 (captopril), an orally active converting enzyme inhibitor, was administered alone or in combination with diuretics to 32 hypertensive patients with different etiologies for 1 to 12 months periods. Twenty-one of these patients had essential hypertension, 4 had renal failure, 2 suffered from renal parenchymal, 2 had malignant, and 1 suffered from renovascular hypertension. One had Cushing's syndrome, and one had a renin-secreting tumor. The daily dose of captopril was from 37.5 to 450 mg per day. The long term hypotensive effect and the correlations of the blood pressure changes and the pre-treatment renin dependency were evaluated. In order to investigate the involvement of factors other than the blockade of the renin-angiotensin axis in the hypotensive mechanism of captopril, endocrinological studies were done on 15 patients who had completed a one year treatment with captopril. The effect of indomethacin on the hypotensive action of captopril in these patients was also studied.<BR>A sustained blood pressure reduction was achieved in most of the 15 patients for over a one year period of treatment, and no severe adverse reactions were observed. The blood pressure reduction significantly correlated with pre-treatment plasma renin activity (PRA) and blood pressure response to the infusion of angiotensin II antagonist within 1 and 2 months of administration, but was no longer noticed after 4 months of treatment. In addition, the correlation of blood pressure changes and the changes in plasma aldosterone concentrations (PAC) also gradually decreased (p<0.0025, 0.005, 0.05, n.s. at 1, 2, 4 and 12 months, respectively). The following measurements were compared among the groups of the 15 patients treated with captopril alone or in combination with diuretics, normotensive patients, hypertensive non-treated patients and hypertensives treated with thiazide alone for at least one year, with regards the renin-angiotensin system (PRA, PAC, plasma angiotensin I and II, urinary aldosterone excretion), serum converting enzyme activity, plasma and urinary catecholamine (adrenaline and noradrenaline), plasma bradykinin, and plasma prostaglandin E and F. Both captopril-treated groups had a significant elevation of angiotensin I and a reduction of aldosterone excretion when compared with the other groups. In spite of a sustained reduction of blood pressure, plasma catecholamine did not show a significant elevation in both captopril-treated groups, and urinary catecholamine was suppresed in the captopril-alone group. Serum converting enzyme activity, plasma bradykinin, kallikrein and prostaglandins did not differ among all groups. However, the administration of indomethacin (150mg/day for one week) significantly abolished the hypotensive action of captopril. From the present study, the sustained reduction of aldosterone excretion and the elevation of serum potassium indicate the persistent blockade of angiotensin II as one of the hypotensive factors in the long-term treatment with captopril. However, since the correlations of the changes in blood pressure and the pre-treatment renin dependency gradually diminished in spite of the significant fall in blood pressure, other hypotensive mechanisms should be considered. Although plasma prostaglandins did not show a significant elevation, the fact that indomethacin blunted the hypotensive action of captopril suggests that renal or local prostaglandins may play a role in the long-term efficacy of captopril. Sympathetic activity may also be suppressed by captopril and participate in its hypotensive efficacy.
日本内分泌学会の論文

変換酵素抑制薬カプトプリル長期投与による降圧効果ならびに降圧機作に関する内分泌学的研究

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