変換酵素抑制剤カプトプリルの降圧機序解明に関する臨床的研究

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SQ 14,225, a potent and specific inhibitor of angiotensin I converting enzyme, has been demonstrated to be an effective antihypertensive agent. Because angiotensin I converting enzyme is identical to kiniase II which degradates kinin, both the blockade of vasoconstrictor, angiotensin II and the accumulation of vasodilator, bradykinin may contribute to the blood-pressure-lowering effect of captopril. Our previous study of captopril revealed that its antihypertensive effect correlates significantly with pre-treatment plasma renin activity (PRA) and blood pressure response to the infusion of angiotensin II antagonist. However, this correlation was significant in acute single doses in one or 2 months of administration but was no longer noticed after 4 months of treatment. This indicates that the blockade of the renin-angiotensin-aldosterone system is the major mechanism for the chronic antihypertensive effect within 2 months of treatment with captopril. The present study is to investigate the changes of the renin-angiotensin-aldosterone system and other hormonal factors to assess the possible involvement of other mechanisms in the long term effectiveness of captopril.<BR>Captopril was administered, alone or in combination with diuretics, to 32 hypertensive patients for 1 to 4 month periods. Twenty-one of these patients had essential 4 renal failure, 2 renal parenchymal, 2 malignant, 1 renovascular hypertension. One had Cushing's syndrome and one had a renin-secreting tumor. The daily dose of captopril ranged from 37.5 to 450 mg per day.<BR>A decrease of mean arterial blood pressure (MBP) of more than 13 mmHg after treatment was considered effective. The mean reduction of the MBP was 16 ± 3 -0 ± 4 (mean S.E.) captopril alone and 25 ± 4 -32 ± 5 mmHg in combination therapy. The combination of captopril with diuretics caused more reduction than captopril alone.<BR>PRA, plasma aldosterone concentration (PAC), 24 hour urinary aldosterone and catecholamine excretion (noradrenaline and adrenaline) urinary kallikrein, serum and urinary electrolytes, and creatinine clearance were compared between responders who had a decrement of MBP which exceeded 13 mmHg and non-responders who did not. Compared to non-responders, responders not only had a higher control PRA and a significant elevation of PRA at one month treatment, but also showed persistent fall of PAC, urinary aldosterone secretion and increased plasma potassium. The reductio, urinary sodium and potassium, serum sodium and endogenous creatinine clearance did not show significant differences either before or after treatment.<BR>These findings together with our previous study suggest that the antihypertensive effect of captopril is related to the pretreatment plasma renin level, and the effectiveness of the long term administration of captopril depends mainly on the blockade of angiotensin II formation. However the possibility of the involvement of other mechanisms cannot be ruled out.
日本内分泌学会の論文

変換酵素抑制剤カプトプリルの降圧機序解明に関する臨床的研究

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