NAD(P)H oxidase-derived hydrogen peroxide mediates endothelial nitric oxide production in response to angiotensin II

Hua Cai, Zongming Li, Sergey Dikalov, Steven M. Holland, Jinah Hwang, Hanjoong Jo, Samuel C. Dudley, David G. Harrison

Research output: Contribution to journalArticlepeer-review

167 Scopus citations


Recently, it has been shown that the exogenous addition of hydrogen peroxide (H2O2) increases endothelial nitric oxide (NO.) production. The current study is designed to determine whether endogenous levels of H2O2 are ever sufficient to stimulate NO. production in intact endothelial cells. NO production was detected by a NO.. specific microelectrode or by an electron spin resonance spectroscopy using Fe2+-(DETC)2 as a NO.·specific spin trap. The addition of H2O2 to bovine aortic endothelial cells caused a potent and dose-dependent increase in NO. release. Incubation with angiotensin II (10-7 mol) elevated intracellular H2O2 levels, which were attenuated with PEG-catalase. Angiotensin II increased NO. production by 2-fold, and this was prevented by Losartan and by PEG-catalase, suggesting a critical role of AT1 receptor and H2O2 in this response In contrast, NO. production evoked by either hradykinin or calcium ionophore A23187 was unaffected by PEG-catalase. As in bovine aortic endothelial cells, angiotensin II doubled NO. production in aortic endothelial cells from C57BL/6 mice but had no effect on NO. production in endothelial cells from p47phox-/- mice. In contrast, A23187 stimulated NO. production to a similar extent in endothelial cells from wild-type and p47phox-/ mice. In summary, the present study provides direct evidence that endogenous H2O2 derived from the NAD(P)H oxidase, mediates endothelial NO. production in response to angiotensin II. Under disease conditions associated with elevated levels of angiotensin II, this response may represent a compensatory mechanism. Because angiotensin II also stimulates O2-production from the NAD(P)H oxidase, the H2O2 stimulation of NO. may facilitate peroxynitrite formation in response to this octapeptide.

Original languageEnglish (US)
Pages (from-to)48311-48317
Number of pages7
JournalJournal of Biological Chemistry
Issue number50
StatePublished - Dec 13 2002


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