Gp91phox-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II

Shintaro Kinugawa, Juhua Zhang, Eric Messina, Erin Walsh, Harer Huang, Pawel M. Kaminski, Michael S. Wolin, Thomas H. Hintze

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)H862-H867
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number2 58-2
DOIs
Publication statusPublished - Aug 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Gp91<sup>phox</sup>-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II'. Together they form a unique fingerprint.

  • Cite this