Received for publication December 20, 2005.
Revised January 26, 2006.
Accepted for publication January 30, 2006.

Segmental differences in the roles of rho-kinase and protein kinase C in mediating vasoconstriction

Abstract

Rho-kinase and protein kinase C (PKC) have each been reported to mediate vasoconstriction via calcium sensitization. However, the relative contributions of these two kinases to vascular contraction, and whether their roles vary between large and small arteries, are largely unknown. We therefore assessed the relative roles of rho-kinase and PKC in mediating vasoconstriction in arteries from three segments of the aortic and mesenteric vasculature. We studied contractile responses of rat isolated aorta (diameter2mm), superior mesenteric artery (SMA, 1.5mm) and second order branches of the superior mesenteric artery (BMA, 300µm). The roles of rho-kinase and PKC in mediating contractile responses to phenylephrine, U46619, and potassium chloride (KCl), were assessed by using the rho-kinase inhibitor, Y-27632 (1 and 10 µM) and the PKC inhibitor, Ro 31-8220 (5 µM). Contractile responses of aorta and SMA were reduced by either 1 or 10 µM Y-27632 (P<0.05) whereas responses of BMA were reduced by 10 µM (P<0.05), but not 1 µM Y-27632. In contrast, Ro 31-8220 partly reduced contractile responses in aorta and SMA (P<0.05), but completely abolished responses of BMA (P<0.05). Co-treatment with Y-27632 and Ro 31-8220 markedly attenuated contractile responses to phenylephrine and KCl in all vessels, but had only a moderate inhibitory effect on responses to U46619 in aorta and SMA. Thus, contractile responses of the larger arteries can involve both rho-kinase and PKC, to varying degrees. Conversely, contractile responses of small mesenteric resistance arteries appear to be mediated exclusively by PKC, with no apparent role for rho-kinase.

Key words: endothelium, mesenteric artery, phenylephrine, protein kinase C, rho kinase, vasoconstriction

This article has been cited by other articles:

				S. Rattan and C. A. Patel Selectivity of ROCK inhibitors in the spontaneously tonic smooth muscle Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G687 - G693. [Abstract] [Full Text] [PDF]

				K. J. Allahdadi, L. C. Duling, B. R. Walker, and N. L. Kanagy Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKC{delta} Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H920 - H927. [Abstract] [Full Text] [PDF]

				K. J. Allahdadi, B. R. Walker, and N. L. Kanagy ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2911 - H2918. [Abstract] [Full Text] [PDF]

				S. A. Barman Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L472 - L479. [Abstract] [Full Text] [PDF]