title: Rho-kinase inhibitor reduces hypersensitivity to ANG II in human mesenteric arteries retrieved and conserved under the same conditions as transplanted organs.
abstract: Rho-kinase and GTP-ase Rho are important regulators of vascular tone and blood pressure. The aim of this study was to investigate the role of Rho-kinase in artery reactions induced by angiotensin II (ANG II) and the effects of ischemia-reperfusion injury as well as the function of intra- and extracellular calcium in these reactions. Experiments were performed on mesenteric superior arteries procured from cadaveric organ donors and conserved under the same conditions as transplanted kidneys. The vascular contraction in reaction to ANG II was measured in the presence of Rho-kinase inhibitor Y-27632, after ischemia and reperfusion, in Ca2+ and Ca2+-free solution. The maximal response to ANG II was reduced after ischemia, while an increase was observed after reperfusion. Vascular contraction induced by ANG II was decreased by Y-27632. Y-27632 reduced vascular contraction after reperfusion, both in Ca2+ and Ca2+-free solution. Reperfusion augments vascular contraction in reaction to ANG II. The Rho-kinase inhibitor Y-27632 reduces the hypersensitivity to ANG II after reperfusion mediated by both intra- and extracellular calcium. These results confirm the role of Rho-kinase in receptor-independent function of ANG II and in reperfusion-induced hypersensitivity.
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Szadujkis-Szadurski
authors.affiliation: Department of Transplantation and General Surgery, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Slupski
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szadujkis-Szadurska
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Szadujkis-Szadurski
authors.affiliation: Department of Oncological Urology, Oncology Centre, Bydgoszcz, Poland; Department of Tissue Engineering, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Milosz
authors.initials: M
authors.lastname: Jasinski
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Grzesk
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Polandw.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Grzesk
authors.affiliation: Department of Transplantation and General Surgery, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Woderska
authors.affiliation: Department of Transplantation and General Surgery, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Wlodarczyk
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000804:Angiotensin II / Q000009:adverse effects*; D002102:Cadaver; D002118:Calcium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D008638:Mesenteric Arteries / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism; D014021:Tissue Preservation / Q000379:methods*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; D000804:Angiotensin II; C108830:Y 27632; D054460:rho-Associated Kinases; D002118:Calcium