Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney.

Thumbnail Image
Journal Title
Journal ISSN
Volume Title
Krakow Polish Physiological Society
Research Projects
Organizational Units
Journal Issue
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.
Journal Article; Research Support, Non-U.S. Gov't;
DeCS Terms
CIE Terms
Hydrogen Peroxide, Catalase, Hydroxyl Radical, Kidney, Ca2+, Protein kinase C, Sexual Dimorphism, Renal Perfusion Pressure, Catalase, Vasoconstriction, Peróxido de Hidrógeno, Radical Hidroxilo, Riñón, Vasoconstricción
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