"The Physiological Mechanism of Extracellular Calcium- Sensing Receptor Action in the Regulation of Vascular Tone and Blood Pressure"

Abstract

Background: Calcium is the fifth most abundant element in the adult human body. The free ionized calcium (Ca 2+ ) is responsible for a variety of physiological processes and tightly maintained mainly by action of calciotropic hormones and other nutrients. Calcium-sensing receptor (CaSR/CaR) is a cell-surface receptor that responds to, or "senses," extracellular Ca 2+ concentrations in parathyroid, kidney and other tissues. The aim of the review is to get into the fine details of physiologic mechanisms responsible for extracellular calcium-sensing receptor actions in the regulation of vascular tone and blood pressure.Method: Studies were accessed through an electronic web-based search strategy from PubMed, Cochrane Library, Google Scholar, Embase, PsycINFO, and CINAHL by using a combination of search terms.Results/Discussion: The central role of the CaR is the regulation of calcium homeostasis, but it is also expressed in non-calciotropic tissues. It is well known that calcium is an important second messenger and regulator of vascular contractility. An increase in intracellular calcium concentration ([Ca 2+ ]i) in endothelium or in VSMCs exerts opposing influences on blood vessel diameter. Ca 2+ is also an extracellular first messenger and binding of Ca 2+ to CaR mediate biphasic effects with an initial endothelium-independent vasoconstrictions followed by endothelium-dependent relaxations. The vascular endothelium CaR activation mostly results in an activation of the G proteins (G q /11). In parallel, CaR also activates PI4K and carries out the first step in inositol lipids biosynthesis. Endothelial calcium ''waves'' and "puffs" is an initial step required for endothelium-dependent vasorelaxations. The myoendothelial gap junctions have also a major role in electrical spread of hyperpolarization from the ECs to the VMSCs. Furthermore, the main source of NO• in the vasculature is the microvascular endothelium and contribute to cGMP activation in VMSCs and influence vascular reactivity.Conclusion/Perspectives: it is not surprising that CaR is involved in the regulation of such diverse processes as hormone secretion, gene expression, ion channel activity, modulation of inflammation, proliferation, differentiation and apoptosis.