Interactions between endothelin and atrial natriuretic factor in the rat aortic ring preparation.
The potential interaction (s) between atrial natriuretic factor (ANF) and porcine--human endothelin (ET-1) was investigated in the endothelium-denuded rat aortic ring preparation. ET-1 produced a sustained contraction of aortic rings with an ED50 of 3.6 +/- 0.49 x 10(-9) M. Within the concentration range of 10(-9) to 10(-7) M, both rat ANF 103-126 and rat ANF 99-126 when preincubated with tissues reduced the contractile efficacy of ET-1 especially at low concentrations resulting in a small but significant rightward shift of the dose--response curve to ET-1. In contrast, at a concentration of 10(-10) M, rANF 99-126 but not rANF 103-126 produced a significant leftward shift of the dose--response curve to ET-1 and an increase in the maximal developed tension for the dose--response curve to ET-1. For tissues incubated in the absence of extracellular calcium or in the presence of the calcium channel blocker nifedipine (5 x 10(-7) M), both ANF derivatives produced a dose-dependent decrease in the maximum contraction, but no change in potency to ET-1. Addition of either rANF 103-126 or rANF 99-126 to tissues maximally contracted with ET-1 resulted in relaxation, reaching a maximum of 70%. The ED50 values for relaxation were 2.7 +/- 0.51 x 10(-8) and 3.5 +/- 0.60 +/- 10(-8) M for rANF 103-126 and rANF 99-126, respectively. ET-1 did not interact with biologically responsive and clearance receptors for ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Bolger
G
G
Department of Pharmacology, Bio-Méga Inc., Laval Québec, Canada.
Liard
F
F
Krogsrud
R
R
Welchner
E
E
Jaramillo
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction; D014664:Vasodilation
D016232:Endothelins; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor