Possible mechanisms underlying the vasorelaxant response to atrial natriuretic factor.
Synthetic analogs of atrial natriuretic factor (ANF) have been utilized to assess possible mechanisms underlying the vasorelaxation response to this peptide. ANF is a potent relaxant of aortic smooth muscle contracted by a variety of agonists and low (e.g., 20 mM) but not high (e.g., greater than or equal to 80 mM) levels of extracellular K+. The relaxation does not require the presence of a functional endothelium and is temporally associated with the elevation of tissue levels of cyclic GMP resulting from a direct activation of particulate guanylate cyclase. The ANF-induced relaxation is not associated with membrane hyperpolarization but may be related to an alteration of Ca2+ handling by the vascular smooth muscle cell via inhibition of agonist-induced Ca2+ translocation, stimulation of Ca2+ extrusion, or interference with Ca2+ release from intracellular storage sites. ANF displays regional vasorelaxant selectivity in vitro (e.g., arteries vs. veins, central vs. peripheral arteries), which may be, in part, a function of an altered distribution of high-affinity receptors and/or particulate guanylate cyclase. These latter developments may explain the discrepancy between the potent vasorelaxant response in vitro and the modest or limited vasodilator response in whole-animal experiments.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000032:analysis; D013045:Species Specificity; D014664:Vasodilation / Q000187:drug effects*
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium