gp91-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II

Kinugawa, Shintaro, Juhua Zhang, Eric Messina, Erin Walsh, Harer Huang, Pawel M. Kaminski, Michael S. Wolin, and Thomas H. Hintze. gp91-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II. Am J Physiol Heart Circ Physiol 289: H862–H867, 2005. First published March 18, 2005; doi:10.1152/ajpheart.00076.2005.—We have previously reported that ANG II stimulation increased superoxide anion (O2 ) through the activation of NAD(P)H oxidase and inhibited nitric oxide (NO)-dependent control of myocardial oxygen consumption (MV̇O2) by scavenging NO. Our objective was to investigate the role of NAD(P)H oxidase, especially the gp91 subunit, in the NO-dependent control of MV̇O2. MV̇O2 in mice with defects in the expression of gp91 [gp91( / )] was measured with a Clark-type oxygen electrode. Baseline MV̇O2 was not significantly different between wildtype (WT) and gp91( / ) mice. Stimulation of NO production by bradykinin (BK) induced significant decreases in MV̇O2 in WT mice. BK-induced reduction in MV̇O2 was enhanced in gp91( / ) mice. BK-induced reduction in MV̇O2 in WT mice was attenuated by 10 8 mol/l ANG II, which was restored by coincubation with Tiron or apocynin. In contrast to WT mice, BK-induced reduction in MV̇O2 in gp91( / ) mice was not altered by ANG II. There was a decrease in lucigenin (5 10 6 mol/l)-detectable O2 in gp91( / ) mice compared with WT mice. ANG II resulted in significant increases in O2 production in WT mice, which was inhibited by coincubation with Tiron or apocynin. However, ANG II had no effect on O2 production in gp91( / ) mice. Histological examination showed that the development of abscesses and/or the invasion of inflammatory cells occurred in lungs and livers but not in hearts and kidneys from gp91( / ) mice. These results indicate that the gp91 subunit of NAD(P)H oxidase mediates O2 production through the activation of NAD(P)H oxidase and attenuation of NO-dependent control of MV̇O2 by ANG II.