INHIBITION OF ATRIAL-NATRIURETIC-PEPTIDE EXCRETORY ACTION BY BRADYKININ

We examined whether the excretory effect of atrial natriuretic peptide could be antagonized by intravenously administered bradykinin or by e levated endogenous kinin levels attained during converting enzyme inhi bition. Urinary volume and sodium and potassium excretion were determi ned every 20 minutes in female, anesthetized Sprague-Dawley rats (weig ht, 0.19 to 0.22 kg) infused with 10 mu L/min isotonic glucose. In som e experiments, urinary cGMP content was measured by radioimmunoassay. Two intravenous boluses of 209 pmol (0.5 mu g) atrial natriuretic pept ide were given before and after the injection of test substances, and the response ratio was used to quantify inhibition. Single injections of 94.3 or 142 pmol (100 or 150 ng) bradykinin, 3 minutes prior to atr ial natriuretic peptide, inhibited the excretion of water, sodium, and potassium by 70%, 75%, and 50%, respectively. Larger (236 to 472 pmol ) or smaller (23.6 to 47.2 pmol) bradykinin doses were ineffective. No ne of the bradykinin doses tested affected basal urinary output, syste mic pressure, or the modest depressor effect of atrial natriuretic pep tide. The anti-atrial natriuretic peptide effect of bradykinin was com pletely prevented by the kinin receptor antagonist Hoe 140. Converting enzyme inhibition with ramipril (96 nmol IV) also blunted atrial natr iuretic peptide diuresis and natriuresis by 70% and reduced urinary cG MP excretion by 50%. These effects of ramipril were mediated by endoge nous kinin accumulation, since they were abolished by pretreatment wit h Hoe 140. It is concluded that intrarenal kinins modulate the renal a ctions of atrial natriuretic peptide, and at a precise concentration b radykinin strongly antagonizes atrial natriuretic peptide by preventin g its transduction mechanism.