Role of kinins in basal and furosemide-stimulated renin secretion.

OBJECTIVE

There is evidence that kinins contribute to some of the renal, cardiovascular, and endocrine effects of the diuretic furosemide. The aim of the present study was to investigate the role of kinins in the regulation of renin secretion, blood pressure, and heart rate under resting conditions and after administration of furosemide.

METHODS

The effects of icatibant, a potent, specific, and long-lasting bradykinin B2 receptor antagonist, on resting renin secretion, blood pressure, and heart rate, and on the responses of these variables to administration of furosemide, were investigated in conscious, chronically prepared rabbits.

RESULTS

Injection of icatibant in doses of 0.1 and 1.0 mg/kg blocked the hypotensive response to intravenous injections of bradykinin completely. The lower dose of icatibant decreased plasma renin activity in some animals, but did not alter their blood pressure or heart 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 the blood pressure or heart rate. Injection of furosemide (2 mg/kg) caused a sustained increase i plasma renin activity from 6.7 +/- 1.6 to 15.9 +/- 3.3 ng/ml/2h (P < 0.01), a transient increase in mean arterial 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). Neither dose of icatibant altered the cardiovascular and renin responses to furosemide.

CONCLUSIONS

These results provide evidence that bradykinin B2 receptors participate in the regulation of resting renin secretion, but not in the renin secretory or heart rate responses to furosemide.