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The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on the renal kallikrein-kinin system and renal hemodynamics was studied in anesthetised dogs for 45 min after captopril administration. ACE inhibition was confirmed by increases in blood angiotensin I (AI) and plasma renin activity and a 20-fold decrease in sensitivity of the blood pressure and renal blood flow dose-response curves to AI. Captopril (1.5 mg . kg-1, i.v.) led to an increase in renal blood flow of 56 +/- 13 ml/min-1 (P less than .01) despite a fall in mean arterial pressure of 17 +/- 5 mm Hg (P less than 0.005). Glomerular filtration rate did not change whereas the filtration fraction decreased (p less than 0.005). The hypotension and renal vasodilation were accompanied by an increase in urinary kinin excretion (P less than .025) but no acute change in circulating kinins or urinary kallikrein excretion. Urine volume and urinary sodium and potassium excretion increased. To determine the contribution of the renin-angiotensin system to these hemodynamic changes, were gave captopril to a further group of dogs during a continuous infusion of the competitive angiotensin II (AII) receptor antagonist sar1ile8-AII (2.5 micrograms/kg/min). Subsequent ACE inhibition was still associated with an increase in renal blood flow of 35 +/- 17 ml/min-1 (P less than 0.05), decrease with a mean arterial pressure by 11 +/- 4 mm Hg (P less than 0.025). These results suggest that ACE inhibition increases levels of intra-renal kinins and that decreased degradation of these tissue vasodilator peptides may contribute significantly to the acute renal vasodilation and hypotensive effect of captopril.

Angiotensin-converting enzyme kininase II reduces bradykinin metabolism in vitro and in vivo. However, consistent changes in circulating bradykinin levels after the angiotensin-converting enzyme inhibitor captopril have not been reported. The kallikrein-kinin system has been suggested to be a local hormonal system concerned with regional blood flow, and hence circulating levels may not reflect local tissue levels of kinins. Anesthetized dogs given captopril had a significant increase in urinary kinin excretion without a change in circulating bradykinin levels or in urinary kallikrein. These changes in renal kinins were accompanied by a decrease in blood pressure and renal vasodilation. The hypotension and renal vasodilation produced by captopril were not attenuated either by pretreatment with the angiotension receptor antagonist Sar1-Ileu8-angiotensin II or by reduction of endogenous prostaglandin production with indomethacin. Postischemic renal vasodilation after temporary renal artery occlusion was also associated with increased urinary kinin levels. These results demonstrate that captopril effectively inhibits renal angiotensin-converting enzyme and that the renal kallikrein-kinin system may play an important role in regulating the renal vasculature and may contribute to the renal hemodynamic effects of captopril. Many polypeptide hormone membrane receptors are self-regulated by endogenous tissue concentrations of the peptide hormone. Infusions of bradykinin into rats reduced specific bradykinin receptors. A similar decrease in bradykinin receptor numbers without change in receptor affinity was demonstrated after captopril administration. These results provide indirect evidence that angiotensin-converting enzyme/kininase inhibition by captopril increases local tissue concentration of kinins, which may contribute to the hypotensive effect.