Extracellular Ca2+ promotes nitric oxide production via Ca2+-sensing receptor-Gq/11 protein-endothelial nitric oxide synthase signaling in human vascular endothelial cells

Abstract

This study examined the possible involvement of Ca²⁺-sensing receptor (CaSR) in nitric oxide (NO) production in human vascular endothelial cells. Extracellular Ca²⁺ elevated the intracellular Ca²⁺ concentration, the endothelial NO synthase (eNOS) phosphorylation level, and NO release from the cells. These responses were inhibited by a CaSR antagonist and a G_q/11 protein inhibitor. Application of an endothelial cell suspension induced vasorelaxation in isolated rat thoracic aorta precontracted by phenylephrine. Adding an NO scavenger to the organ bath abolished this vasorelaxation response. These results suggest that extracellular Ca²⁺ promotes NO generation via CaSR- and G_q/11 protein-mediated eNOS activation.

Keywords: Ca(2+)-sensing receptor; Endothelial nitric oxide synthase; Extracellular Ca(2+).