Role of the calcium-sensing receptor in regulating vascular function

Abstract

Functional expression of the calcium-sensing receptor (CaSR) in calcitropic tissues, for example, parathyroid glands and kidneys, is important for maintaining Ca²⁺ homeostasis. It is also established that the CaSR is present in tissues previously thought to be noncalcitropic and this review discusses the role of the CaSR in vascular function, focusing mainly on contractility but also outlining its role in cell proliferation and calcification. Stimulation of the CaSR by extracellular Ca²⁺ concentration ([Ca²⁺]_o) on perivascular sensory nerves and vascular endothelial cells is associated with vasodilatation through the release of vasoactive substances and stimulation of IK_Ca channels and nitric oxide synthesis, respectively, which mediate endothelium-derived hyperpolarizations and activation of BK_Ca channels and K_ATP channels in vascular smooth muscle cells (VSMCs). CaSR-induced vasoconstrictions are mediated by the CaSR expressed in VSMCs, which are coupled to the G_q/11 protein-coupled pathway. In addition, the CaSR expressed on VSMCs also regulates proliferation and calcification. Consequently, the CaSR has been implicated in regulating systemic and pulmonary blood pressure and calcimimetics and calcilytics are potential therapeutic targets for cardiovascular diseases, such as hypertension, pulmonary artery hypertension, and atherosclerosis.