Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats.
In both normally hydrated and volume-expanded rats, there was a biphasic effect of corticotropin-releasing hormone (CRH) (1-10 microgram, i.v.) on renal function. Within the first hour, CRH caused antidiuresis, antinatriuresis, and antikaliuresis together with reduction in urinary cGMP output that, in the fourth hour, were replaced by diuresis, natriuresis, and kaliuresis accompanied by increased cGMP output. Plasma arginine vasopressin (AVP) concentrations increased significantly within 5 min, reached a peak at 15 min, and declined by 30 min to still-elevated values maintained for 180 min. Changes in plasma atrial natriuretic peptide (ANP) were the mirror image of those of AVP. Plasma ANP levels were correlated with decreased ANP in the left ventricle at 30 min and increased ANP mRNA in the right atrium at 180 min. All urinary changes were reversed by a potent AVP type 2 receptor (V(2)R) antagonist. Control 0.9% NaCl injections evoked an immediate increase in blood pressure and heart rate measured by telemetry within 3-5 min. This elevation of blood pressure was markedly inhibited by CRH (5 microgram). We hypothesize that the effects are mediated by rapid, direct vasodilation induced by CRH that decreases baroreceptor input to the brain stem, leading to a rapid release of AVP that induces the antidiuresis by direct action on the V(2)Rs in the kidney. Simultaneously, acting on V(2)Rs in the heart, AVP inhibits ANP release and synthesis, resulting in a decrease in renal cGMP output that is responsible for the antinatriuretic and antikaliuretic effects.
Gutkowska
J
J
Laboratory of Cardiovascular Biochemistry, Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Department of Medicine, University of Montreal, Montreal, PQ, Canada H2W 1T8. jolanta.gutkowska@umontreal.ca
Jankowski
M
M
Mukaddam-Daher
S
S
McCann
S M
SM
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood* / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D065092:Antidiuretic Hormone Receptor Antagonists; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor; D003346:Corticotropin-Releasing Hormone; D006152:Cyclic GMP; D011188:Potassium