Differential roles of rho‐kinase and protein kinase C (PKC) in contractile responses of rat aorta and mesenteric artery

Abstract

Rho-kinase and protein kinase C (PKC) have each been shown to mediate vasoconstriction via calcium sensitization in response to G protein-coupled receptor (GPCR) stimulation. However, the relative contributions of rho-kinase and PKC to vascular contraction, and whether their roles vary between large and small blood vessels, are not well understood. We therefore assessed the relative roles of rho-kinase and PKC in mediating vascular contraction in isolated rings of aorta (Ao), superior mesenteric artery (MA) and second order branches of the superior mesenteric artery (BMA), from male Sprague-Dawley rats. We tested the effects of the rho-kinase inhibitor, Y-27632 (1μM), and the PKC inhibitor, Ro 31-8220 (5μM) either alone or in combination, on contractile responses to phenylephrine (PE). Maximum responses of Ao and MA to PE were reduced by Y-27632 (n=3-10; P<0.05), whereas responses of BMA were unaffected. Ro 31-8220 partly reduced contractile responses to PE in Ao and MA (n=3-10; P<0.05). Responses of BMA were completely abolished by Ro 31-8220 (n=6-7; P<0.05), and endothelial removal did not alter this effect. Co-treatment with Y-27632 and Ro 31-8220 abolished contractile responses in all arteries. Thus, contractile responses of Ao and MA to PE can involve both rho-kinase and PKC, to varying degrees. In BMA, PKC appears to exclusively mediate these contractile responses, with no apparent role for rho-kinase.