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

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Date
2010-06
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Krakow Polish Physiological Society
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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.
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Journal Article; Research Support, Non-U.S. Gov't;
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Keywords
Hydrogen Peroxide, Catalase, Hydroxyl Radical, Kidney, Ca2+, Protein kinase C, Sexual Dimorphism, Renal Perfusion Pressure, Catalase, Vasoconstriction, Peróxido de Hidrógeno, Radical Hidroxilo, Riñón, Vasoconstricción
Citation
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