title: Hyperosmolar glucose induces vasoconstriction through Rho/Rho-kinase pathway in the rat aorta.
abstract: Rho/Rho-kinase signalling pathway plays a substantial role in vascular contractions. In this study, we investigated any roles of Rho/Rho-kinase pathway in the vasoconstriction of the rat conductance and capacitance vessels by hyperosmolar glucose solution. Isolated aortic, mesenteric and renal rings were suspended and exposed to hyperosmolar glucose, sucrose and NaCl in the organ chambers filled with Krebs solution gassed with 95% O2 and 5% CO2 and maintained at 37 °C. The effect of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 10(-5) M), was tested on the contraction induced by hypertonic solutions. Endothelial integrity was also assessed after hyperosmolar glucose exposure. Moreover, the activity and expression of Rho-kinase (ROCK-2) as well as RhoA translocation were detected by Western blotting and enzyme-linked immunosorbent assay-based RhoA activity detection method detection kit. The vessels produced substantial contractions in response to hyperosmolar solutions. Y-27632 significantly reduced hyperosmolarity-induced vasoconstrictions (P < 0.05). Phosphorylation of myosin-phosphatase target 1 increased after hyperosmolar glucose exposure, and this phosphorylation was significantly decreased by Y-27632 (P < 0.05) in the aorta. Furthermore, RhoA translocation but not ROCK-2 expression markedly increased by hyperosmolar glucose solution. These results may indicate that hyperosmolarity could induce vasoconstriction through Rho/Rho-kinase signalling.
authors.affiliation: Department of Pharmacology, Medical Faculty, Mersin University, Campus Yenişehir 33169, Mersin, Turkey. unisfarma@yahoo.com
authors.forename: İsmail
authors.initials: İ
authors.lastname: Ün
authors.forename: A Hakan
authors.initials: AH
authors.lastname: Kurt
authors.forename: Kansu
authors.initials: K
authors.lastname: Büyükafşar
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D021381:Protein Transport; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000577:Amides; D011725:Pyridines; C108830:Y 27632; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D020742:rhoA GTP-Binding Protein; D005947:Glucose