Integration of hypoxic dilation signaling pathways for skeletal muscle resistance arteries

Jefferson C. Frisbee, Kristopher G. Maier, J R Falck, Richard J. Roman, Julian H. Lombard

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Mediator contributions to hypoxic dilation of rat gracilis muscle resistance arteries were determined by measuring dilation, vascular smooth muscle hyperpolarization, and metabolite production after incremental hypoxia. Nitric oxide (NO) synthase inhibition abolished responses to mild hypoxia, whereas COX inhibition impaired responses to more severe hypoxia by 77%. Blocking 20-hydroxyeicosatetraenoic acid (20-HETE) impaired responses to moderate hypoxia. With only NO systems intact, responses were maintained with mild hypoxia (88% normal) mediated via KCa channels. When only COX pathways were intact, responses to moderate-severe hypoxia were largely retained (79% of normal) mediated via KATP channels. Vessel responses to moderate hypoxia were retained with only 20-HETE systems intact mediated via KCa channels. NO production increased 5.6-fold with mild hypoxia; greater hypoxia was without further effect. With increased hypoxia, 20-HETE levels fell to 40% of control values. 6-keto-PGF levels were not altered with mild hypoxia, but increased 4.6-fold with severe hypoxia. These results suggest vascular reactivity to progressive hypoxia represents an integration of NO production (mild hypoxia), PGI2 production (severe hypoxia), and reduced 20-HETE levels (moderate hypoxia).

Original languageEnglish (US)
Pages (from-to)R309-R319
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume283
Issue number2 52-2
DOIs
StatePublished - Jan 1 2002

Keywords

  • 20-hydroxyeicosatetraenoic acid
  • Cytochrome P-450 4a enzymes
  • Microvessels
  • Nitric oxide
  • Oxygen-induced vascular reactivity
  • Prostacyclin
  • Skeletal muscle microcirculation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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