Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney.
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.
Moreno
J M
JM
Departamento de Fisiologia, Facultad de Medicina, Granada, Spain.
Rodriguez Gomez
I
I
Wangensteen
R
R
Perez-Abud
R
R
Duarte
J
J
Osuna
A
A
Vargas
F
F
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
D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D002374:Catalase