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 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 485
  • Publication Date: 2004
  • Doi Number: 10.1016/j.ejphar.2003.11.076
  • Page Numbers: pp.263-268


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.