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

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 ANPinduced activation of the particulate guanylate cyclase, and that this may be the cause of the blunted cGMP response of SHR VSMCs to ANP. Am J Hypertens 1989;2:111–113