Vascular NAD(P)H oxidase is distinct from the phagocytic enzyme and modulates vascular reactivity control

Heraldo P. Souza, Francisco R.M. Laurindo, Roy C. Ziegelstein, Carlos O. Berlowitz, Jay L. Zweier

Research output: Contribution to journalArticlepeer-review

Abstract

An NAD(P)H oxidase has been hypothesized to be the main source of reactive oxygen species (ROS) in vessels; however, questions remain about its function and similarity with the neutrophil oxidase. Therefore, vascular superoxide generation was measured by electron paramagnetic resonance spectroscopy using the spin-trap 5,5′-dimethly-pyrroline-N-oxide in aortas from wild-type (WT) and gp91phox-deficient mice (gp91phox-/-), which do not have a functioning neutrophil NADPH oxidase. There was no significant difference between radical adduct formation by WT or gp91phox-/- mouse aortas either at baseline or after stimulation with NADPH or NADH. Also, spin-adduct formation was identical in the 100,000-g pellets obtained from WT and gp91phox-/- mouse aortas. SOD mimetics and the flavoenzyme inhibitor diphenyleneiodonium blocked spin-adduct formation from both intact vessels and particulate fractions. Other pharmacological inhibitors of metabolic pathways involved in ROS generation had no effect on this phenomenon. To examine the role of this enzyme in vascular tone control, aortic rings were suspended in organ chambers and preconstricted with phenylephrine to reach half-maximal contraction. Exposure to NADPH elicited a 20% increase in vascular tone, which was decreased by SOD mimetics in a concentration-dependent manner, suggesting that superoxide was responsible for this phenomenon. NADH had no effect on vascular tone. Thus superoxide is generated in the vessel wall by an NAD(P)H-dependent oxidase, which modulates vascular contractile tone. This enzyme is structurally and genetically distinct from the neutrophil NADPH oxidase.

Original languageEnglish (US)
Pages (from-to)H658-H667
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
DOIs
StatePublished - Feb 2001

Keywords

  • Diphenyleneiodonium
  • Electron paramagnetic resonance
  • Gp91 knockout mice
  • NADH
  • NADPH
  • Reactive oxygen species
  • Superoxide
  • Superoxide dismutase

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Vascular NAD(P)H oxidase is distinct from the phagocytic enzyme and modulates vascular reactivity control'. Together they form a unique fingerprint.

Cite this