HYPOTENSIVE ACTION OF ANGIOTENSIN-I CONVERTING ENZYME-INHIBITOR (SQ-14,225) IN NEPHRECTOMIZED DOGS

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Abstract
The contribution of the renin-angiotensin system to the acute depressor action of angiotensin I-converting enzyme inhibitor was clarified and the role of the kidney under such conditions was assessed. In anesthetized dogs, intrarenal and i.v. infusion of SQ 14,225 at a rate 0.5 mg/min resulted in a significant and similar fall in systemic blood pressure. This effect was not altered even when the receptors were occupied by exogenous angiotensin II (100 ng/min i.v.). Apparently, the renin-angiotensin system plays a relatively minor role in the blood pressure reduction in normotensive anesthetized dogs. Six hours after nephrectomy, when the plasma renin activity had become negligible, SQ 14,225 produced a significant fall in systemic blood pressure. The magnitude was not statistically different from that noted during i.v. infusion of SQ 14,225 in the dog with both kidneys intact. The effect was abolished after inhibition of kallikrein, as induced by aprotinin (10,000 kallikrein inhibitory unit/kg i.v., 10,000 kallikrein inhibitory unit/kg.cntdot.h i.v.) The possibility that the extrarenal kallikrein-kinin system contributes to the acute hypotensive action of SQ 14,225 rather than to the inhibition of the metabolism of angiotensin has to be given attention.