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 Ca ¹, 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. Am J Hypertens 1989;2:111-113.