Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide

Xiaosun Zhou, H. Glenn Bohlen, Joseph L. Unthank, Steven J. Miller

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Previous work in our laboratory showed increased basal periarterial nitric oxide (NO) and H2O2 concentrations in the spontaneously hypertensive rat, characterized by oxidant stress, as well as impaired flow-mediated NO production that was corrected by a reduction of periarterial H2O2. Aging is also associated with an increase in vascular reactive oxygen species and results in abnormal vascular function. The current study was designed to assess the role of H2O2 in regulating NO production during vascular aging. In vivo, real-time NO and H 2O2 concentrations were measured by microelectrodes in mesenteric arteries of retired breeder (aged; 8-12 mo) and young (2 to 3 mo) Wistar-Kyoto rats under conditions of altered flow. The results in aged rats revealed elevated basal NO (1,611 ± 286 vs. 793 ± 112 nM, P < 0.05) and H2O2 concentrations (16 < 2 vs. 9 < 1 μM, P < 0.05) and a flow-mediated increase in H2O2 but not NO production. Pretreatment of aged rats with the antioxidant apocynin lowered both basal H2O2 (8 ± 1 μM) and NO (760 ± 102 nM) to young levels and restored flow-mediated NO production. Similar results were obtained with the NAD(P)H oxidase inhibitor gp91ds-tat. In addition, acute incubation with topical polyethylene-glycolated catalase lowered the baseline NO concentration and restored flow-mediated NO production. Taken together, the data indicate that elevated baseline and suppressed flow-mediated NO production in aged Wistar-Kyoto rats are mediated by NAD(P)H oxidase-derived H2O2.

Original languageEnglish (US)
Pages (from-to)H2227-H2233
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number6
DOIs
StatePublished - Dec 2009

Keywords

  • Apocynin
  • Flow mediated
  • Nicotinamide adenine dinucleotide phosphate oxidase inhibition
  • Oxidative stress
  • Wistar-Kyoto rats

ASJC Scopus subject areas

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

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