ROLE OF KININS IN BASAL AND FUROSEMIDE-STIMULATED RENIN SECRETION

Objective There is evidence that kinins contribute to some of the rena l, cardiovascular, and endocrine effects of the diuretic furosemide. T he aim of the present study was to investigate the role of kinins in t he regulation of renin secretion, blood pressure, and heart rate under resting conditions and after administration of furosemide. Methods Th e effects of icatibant, a potent, specific, and long-lasting bradykini n B-2 receptor antagonist, on resting renin secretion, blood pressure, and heart rate, and on the responses of these variables to administra tion of furosemide, were investigated in conscious, chronically prepar ed rabbits. Results Injection of icatibant in doses of 0.1 and 1.0 mg/ kg blocked the hypotensive response to intravenous injections of brady kinin completely. The lower dose of icatibant decreased plasma renin a ctivity in some animals, but did not alter their blood pressure or hea rt rate. The higher dose suppressed resting plasma renin activity from 10.2 +/- 2.2 to 5.6 +/- 1.4 ng/ml/2 h (P < 0.01), without changing th e blood pressure or heart rate. Injection of furosemide (2 mg/kg) caus ed a sustained increase in plasma renin activity from 6.7 +/- 1.6 to 1 5.9 +/- 3.3 ng/ml/2 h (P < 0.01), a transient increase in mean arteria l pressure from 72 +/- 3 to 78 +/- 3 mmHg (P < 0.05), and a sustained increase in heart rate from 228 +/- 8 to 253 +/- 6 bpm (P < 0.01). Nei ther dose of icatibant altered the cardiovascular and renin responses to furosemide. Conclusions These results provide evidence that bradyki nin B-2 receptors participate in the regulation of resting renin secre tion, but not in the renin secretory or heart rate responses to furose mide.