Enhanced release of atrial natriuretic factor by endothelin in atria from hypertensive rats.
Intravenous (bolus) administration of endothelin results in a transient fall in blood pressure that is accentuated in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto normotensive rats (WKY). In attempting to discern possible mechanisms underlying this depressor response, we examined the ability of endothelin to release atrial natriuretic factor (ANF) from isolated, spontaneously contracting atria from SHR and WKY. Isolated right atria were suspended under 3.0 g of resting force in tissue baths with the amount of immunoreactive ANF (irANF) released after exposure to endothelin assessed by radioimmunoassay. Endothelin (10(-8) and 10(-7) M) caused a concentration-dependent increase (1.5-4.5-fold) in the release of irANF, which was significantly greater in atria of SHR compared with WKY. The greater release of irANF in atria of SHR versus WKY was not related to tissue weight or changes in contractile rate or force induced by endothelin. Therefore, endothelin appears to cause a direct release of irANF from rat right atria in vitro. As found for the depressor response in vivo, endothelin is more efficacious in the hypertensive compared with the normotensive atrial preparation. Release of ANF may be important in the hypotensive response to endothelin in vivo.
Winquist
R J
RJ
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Scott
A L
AL
Vlasuk
G P
GP
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D016232:Endothelins; D004730:Endothelium, Vascular / Q000032:analysis; D006325:Heart Atria; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016232:Endothelins; D010455:Peptides; D009320:Atrial Natriuretic Factor