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 elevated endogenous kinin levels attained during converting enzyme inhibition. Urinary volume and sodium and potassium excretion were determined every 20 minutes in female, anesthetized Sprague-Dawley rats (weight, 0.19 to 0.22 kg) infused with 10 microL/min isotonic glucose. In some experiments, urinary cGMP content was measured by radioimmunoassay. Two intravenous boluses of 209 pmol (0.5 micrograms) atrial natriuretic peptide 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 atrial 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. None of the bradykinin doses tested affected basal urinary output, systemic pressure, or the modest depressor effect of atrial natriuretic peptide. The anti-atrial natriuretic peptide effect of bradykinin was completely prevented by the kinin receptor antagonist Hoe 140. Converting enzyme inhibition with ramipril (96 nmol IV) also blunted atrial natriuretic peptide diuresis and natriuresis by 70% and reduced urinary cGMP excretion by 50%. These effects of ramipril were mediated by endogenous kinin accumulation, since they were abolished by pretreatment with Hoe 140. It is concluded that intrarenal kinins modulate the renal actions of atrial natriuretic peptide, and at a precise concentration bradykinin strongly antagonizes atrial natriuretic peptide by preventing its transduction mechanism.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D006152:Cyclic GMP / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D005260:Female; D007705:Kinins / Q000502:physiology; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D013053:Spectrophotometry
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007705:Kinins; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP; D017257:Ramipril; D011188:Potassium; D001920:Bradykinin