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 (MVo2) by scavenging NO. Our objective was to investigate the role of NAD(P)H oxidase, especially the gp91phox subunit, in the NO-dependent control of MVo2. MVo2 in mice with defects in the expression of gp91phox [gp91phox(-/-)] was measured with a dark-type oxygen electrode. Baseline MVo2 was not significantly different between wild-type (WT) and gp91phox(-/-) mice. Stimulation of NO production by bradykinin (BK) induced significant decreases in MVo2 in WT mice. BK-induced reduction in MVo2 was enhanced in gp91phox(-/-) mice. BK-induced reduction in MVo 2 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 MVo2 in gp91 phox(-/-) mice was not altered by ANG II. There was a decrease in lucigenin (5 × 10-6 mol/l)-detectable O2- in gp91phox(-/-) 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 gp91phox(-/-) 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 gp91phox(-/-) mice. These results indicate that the gp91phox subunit of NAD(P)H oxidase mediates O2 - production through the activation of NAD(P)H oxidase and attenuation of NO-dependent control of MVo2 by ANG II.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||2 58-2|
|Publication status||Published - Aug 2005|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)