Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed


Buyukafsar K., Arikan O., Ark M., Secilmis A., Un I., Singirik E.

EUROPEAN JOURNAL OF PHARMACOLOGY, vol.485, pp.263-268, 2004 (SCI-Expanded) identifier identifier identifier

Abstract

Rho-kinase expression was investigated in the rat mesenteric artery and the effects of its inhibitors, (+)-(R)-trans-4-(1-aminoethyl)-N(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632) and fasudil (HA-1077), were examined on the increase in perfusion pressure induced by two different receptor agonists, namely the alpha-adrenoceptor agonist, phenylephrine and, the endothelin ETA and ETB receptor agonist, endothelin-1. Y-27632 and fasudil produced a concentration-dependent decrease in perfusion pressure. There was no difference between the concentration -response lines of these two inhibitors. The maximum decrease in the perfusion pressure induced by 10(-5) M Y-27632 was 85.8 +/- 3.7% when the tone was increased by phenylephrine. However, it was 48.1 +/- 5.4% (P<0.001) when the perfusion pressure was elevated by endothelin-1. Saponin perfusion (100 mg l(-1), for 10 min), which abolished acetylcholine-induced relaxation, did not significantly modify the Y-27632-elicited relaxation. Western blot analysis revealed that rat mesenteric artery expresses, Rho-kinase protein with a molecular weight of approximately 160 kDa. These results show that Rho-kinase enzyme is expressed in rat mesenteric artery and that it contributes to the control of vascular resistance. Moreover, endothelium removal had no marked effect on the vasodilatation induced by Y-27632. In addition, the endothelin-1-induced vasoconstriction was more resistant to the Rho-kinase inhibitors than was that induced by phenylephrine, probably because excitatory endothelin receptors are associated with this signal transduction pathway at a different level from that of alpha-adrenoceptors. (C) 2003 Elsevier B.V. All rights reserved.