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

The vasoconstrictor effect of hydrogen peroxide (h2o2) on isolated perfused rat kidney was investigated. h2o2 induced vasoconstriction in the isolated rat kidney in a concentration-dependent manner. the vasoconstrictor effects of h2o2 were completely inhibited by 1200 u/ml catalase. endothelium-removal potentiated the renal response to h2o2. the h2o2 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 ca2+,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 h2o2,which was virtually suppressed when they were performed together. the pressor response to h2o2 was not affected by: dimethyl sulfoxide (7·10-3 mol/l) plus mannitol (3·10-3 mol/l); intracellular ca2+ 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 h2o2 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 h2o2 in female kidneyswas observed.