title: Possible mechanisms underlying the vasorelaxant response to atrial natriuretic factor.
abstract: 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.
mesh_terms: 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*
chemical_list: D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium