title: Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed.
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 ET(A) and ET(B) 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.
authors.affiliation: Department of Pharmacology, Medical Faculty Mersin University, Campus Yenişehir 33169, Mersin, Turkey. kbuyukafsar@mersin.edu.tr
authors.forename: Kansu
authors.initials: K
authors.lastname: Büyükafşar
authors.forename: Onur
authors.initials: O
authors.lastname: Arikan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ark
authors.forename: Ata
authors.initials: A
authors.lastname: Seçilmiş
authors.forename: Ismail
authors.initials: I
authors.lastname: Un
authors.forename: Ergin
authors.initials: E
authors.lastname: Singirik
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology*; D008642:Mesenteric Veins / Q000187:drug effects / Q000201:enzymology*; D010477:Perfusion / Q000379:methods; D011312:Pressure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases