Cytosolic Ca2+ attenuates ANF-induced cyclic GMP response in vascular smooth muscle cells.

Despite a high density of atrial natriuretic factor (ANF) receptors, cultured vascular smooth muscle cells of the spontaneously hypertensive rat (SHR) manifest a blunted cyclic GMP (cGMP) response to ANF. We explored the role of cytosolic free Ca2+ ([Ca2+]i) in the ANF-induced cGMP response of cultured aortic vascular smooth muscle cells from SHR and two normotensive rat strains: Wistar-Kyoto (WKY) and American Wistar. Exposure to 500 nmol/l A23187 in Ca2+-containing but not in Ca2+-deficient medium resulted in a decline in the ANF-induced cGMP response at maximal ANF concentration (500 nmol/l; SHR from 1004 +/- 98 to 423 +/- 67, P less than 0.001; WKY from 1791 +/- 209 to 625 +/- 90, P less than 0.001; American Wistar from 1496 +/- 125 to 559 +/- 96 fmol/10(6) cells/4 min, P less than 0.001). The same phenomenon was observed by depolarization with 50 mmol/l KCl in Ca2+-containing medium. There were no significant differences among the rat strains in basal levels of [Ca2+]i. If Ca2+ plays a role in the blunted cGMP response to ANF in vascular smooth muscle cells of the SHR, this effect may be exerted by a distinct pool of the ion in the submembrane domain which is associated with the particulate guanylate cyclase system.