Cytosolic Ca2+ Regulation Attenuates ANP-Induced cGMP Response in Vascular Smooth Muscle Cells of the SHR

Abstract

Cultured vascular smooth muscle cells (VSMCs) of the spontaneously hypertensive rat (SHR) show a higher density (Bmax) of ANP receptors and a blunted cyclic (c) GMP response to the hormone. To explore the idea that a higher cytosolic free Ca2+ (Cai2+) may be responsible for a blunted cGMP response to ANP, we examined the effect of raising Cai2+ by the Ca2+-ionophore A23187 or K+ depolarization on the ANP-induced cGMP response. Treatment of VSMCs from the SHR, Wistar-Kyoto rats (WKY), or American Wistar (WIS) rats with A23187 or high K+ resulted in a uniform reduction of the ANP-cGMP response in 1.8 mmol/L Ca2+ medium but not Ca2+-free medium. We conclude that a higher level of Cai2+, probably at the domain adjacent to the membrane, may inhibit ANP-induced activation of the particulate guanylate cyclase, and that this may be the cause of the blunted cGMP response of SHR VSMCs to ANP.