Hypoxic relaxation of penile arteries: Involvement of endothelial nitric oxide and modulation by reactive oxygen species

Dolores Prieto, Pawel M. Kaminski, Zsolt Bagi, Mansoor Ahmad, Michael S. Wolin

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Although obesity-related cardiovascular disease and hypoxia are associated with erectile dysfunction, little is known about the direct effects of hypoxia on penile arteries. In the present study, the effects of acute hypoxia (PO 2 = ∼10 Torr, 20 min) were investigated in isolated penile arteries to determine the influence of endothelium removal, nitric oxide (NO) synthase (NOS), cyclooxygenase (COX), NADPH oxidase, changes in reactive oxygen species (ROS), and a high-fat diet. Hypoxia-relaxed penile arteries contracted with phenylephrine by ∼50%. Relaxation to hypoxia and acetylcholine was reduced by endothelium removal and by inhibition of NOS (Nω- nitro-L-arginine) and COX (indomethacin) but was enhanced by Tempol and by NADPH oxidase inhibition with apocynin and gp91ds-tat. Basal superoxide levels detected by lucigenin chemiluminescence were reduced by Tempol and gp91ds-tat and were enhanced by NOS blockade. Hypoxic relaxant responses were enhanced by catalase and ebselen. Exogenous peroxide evoked relaxations of penile arteries, which were partially inhibited by endothelium removal and by the inhibition of COX and extracellular signal-regulated mitogen-activated protein kinase (MAPK) but enhanced by p38 MAPK blockade. The NO-dependent component of relaxation to hypoxia was impaired in penile arteries from high-fat diet-fed, obese rats associated with increased superoxide production. Thus hypoxic relaxation of penile arteries is partially mediated by endothelial NO in a manner that is normally attenuated by endogenous ROS production. Obesity further increases superoxide production and impairs the influence of NO. Therefore, cardiovascular disease involving decreased NO bioavailability and/or enhanced ROS generation may contribute to erectile dysfunction through impairing the relaxation of penile arteries to hypoxia.

Original languageEnglish (US)
Pages (from-to)H915-H924
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number3
DOIs
StatePublished - Sep 1 2010

Keywords

  • Diet-induced obesity
  • Hypoxia
  • Penile vascular regulation
  • Superoxide

ASJC Scopus subject areas

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

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