title: Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney.
abstract: The vasoconstrictor effect of hydrogen peroxide (H(2)O(2)) on isolated perfused rat kidney was investigated. H(2)O(2) induced vasoconstriction in the isolated rat kidney in a concentration-dependent manner. The vasoconstrictor effects of H(2)O(2) were completely inhibited by 1200 U/ml catalase. Endothelium-removal potentiated the renal response to H(2)O(2). The H(2)O(2) dose-response curve was not significantly modified by administration of the NO inhibitor L-NAME (10(-4) mol/l), whereas it was increased by the non-specific inhibitor of K+-channels, tetraethylammonium (3.10(-3) mol/l). Separately, removal of extracellular Ca(2+), administration of a mixture of calcium desensitizing agents (nitroprusside, papaverine, and diazoxide), and administration of a protein kinase C (PKC) inhibitor (chelerythrine, 10(-5) mol/l) each significantly attenuated the vasoconstrictor response to H(2)O(2), which was virtually suppressed when they were performed together. The pressor response to H(2)O(2) was not affected by: dimethyl sulfoxide (7.10(-5) mol/l) plus mannitol (3.10(-5) mol/l); intracellular Ca(2+) chelation using BAPTA (10(-5) mol/l); calcium store depletion after repeated doses of phenylephrine (10(-5) g/g kidney); or the presence of indomethacin (10(-5) mol/l), ODYA (2.10(-6) mol/l) or genistein (10(-5) mol/l). We conclude that the vasoconstrictor response to H(2)O(2) in the rat renal vasculature comprises the following components: 1) extracellular calcium influx, 2) activation of PKC, and 3) stimulation of pathways leading to sensitization of contractile elements to calcium. Moreover, a reduced pressor responsiveness to H(2)O(2) in female kidneys was observed.
authors.affiliation: Departamento de Fisiologia, Facultad de Medicina, Granada, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Moreno
authors.forename: I
authors.initials: I
authors.lastname: Rodriguez Gomez
authors.forename: R
authors.initials: R
authors.lastname: Wangensteen
authors.forename: R
authors.initials: R
authors.lastname: Perez-Abud
authors.forename: J
authors.initials: J
authors.lastname: Duarte
authors.forename: A
authors.initials: A
authors.lastname: Osuna
authors.forename: F
authors.initials: F
authors.lastname: Vargas
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D002374:Catalase