RT Journal Article T1 Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney. A1 Moreno, J M A1 Rodriguez Gomez, I A1 Wangensteen, R A1 Perez-Abud, R A1 Duarte, J A1 Osuna, A A1 Vargas, F K1 Hydrogen Peroxide K1 Catalase K1 Hydroxyl Radical K1 Kidney K1 Ca2+ K1 Protein kinase C K1 Sexual Dimorphism K1 Renal Perfusion Pressure K1 Catalase K1 Vasoconstriction K1 Peróxido de Hidrógeno K1 Radical Hidroxilo K1 Riñón K1 Vasoconstricción AB 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. PB Krakow Polish Physiological Society SN 0867-5910 YR 2010 FD 2010-06 LK http://hdl.handle.net/10668/865 UL http://hdl.handle.net/10668/865 LA en NO Moreno JM, Rodriguez Gomez I, Wangensteen R, Perez-Abud R, Duarte J, Osuna A, et al. Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney. J. Physiol. Pharmacol. 2010 ; 61(3):325-32 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 7, 2025