Characterizing the role of RGS5 in regulating the myogenic vasoconstrictor response

Abstract

The myogenic response is an established, but poorly understood, mechanism mediated by arteriolar vascular smooth muscle cells (VSMCs). This mechanism is important for both the maintenance of resting vascular tone and the protection of microvascular beds from pressure‐induced injury. Recent evidence supports a role for G‐proteins in mediating this process. Accordingly we hypothesize that regulator of G‐protein signaling proteins that are highly expressed in VSMCs contribute to the regulation of the myogenic response. One such protein, RGS5, is highly expressed in mural cells of arterial vessels and microvasculature. To examine the potential role of RGS5 in the modulation of myogenic constriction, perfusion experiments were conducted on pressurized mesenteric arteries from wild type and RGS5 knockout mice. In support of a role for RGS5 regulating this process, RGS5‐deficient vessels show a trend towards increased sensitivity to elevated pressures and a greater extent of pressure‐induced vascular tone compared to wild type controls. The RGS‐dependent effect on vascular tone is specific to the myogenic response since wild type and knockout vessels responded similarly to phenylepherine and acetylcholine. These data suggest the need to further evaluate the molecular mechanisms whereby RGS5 regulates myogenic constriction in VSMCs.