Altered mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries of hypertensive versus normotensive Dahl rats

Jefferson C. Frisbee, Richard J. Roman, U. Murali Krishna, J R Falck, Julian H. Lombard

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Objective: To determine mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries from normotensive (NT) and hypertensive (HT) Dahl salt-sensitive (SS) rats. Methods: Isolated gracilis arteries (GA) from both rat groups were viewed via television microscopy and vascular responses to a reduction in PO2 from 145 mm Hg to 40 mm Hg were measured with a video micrometer. Responses were determined following endothelium removal and following inhibition of specific biochemical pathways regulating vascular tone. Results: Hypoxic dilation was impaired in HT rats versus NT controls. Endothelium removal abolished hypoxic dilation in NT rats, although a significant dilation to hypoxia remained in vessels from HT animals. Inhibition of cytochrome P450 (CP450) 4A enzymes blunted hypoxic dilation in both groups, while inhibition of epoxyeicosatrienoic acid (EET) production impaired responses in NT rats only. Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) production or blockade of membrane receptors for 20-HETE reduced hypoxic dilation in HT rats, with minimal effects in NT animals. Nitric oxide synthase inhibition had no effect on hypoxic dilation in either group, while cyclooxygenase inhibition significantly reduced this response in both groups. Conclusions: These results suggest that the mechanisms of hypoxic dilation in GA from NT Dahl-SS rats are altered with HT, impairing the response to reduced PO2. While hypoxia induces substantial prostanoid release in both groups, the role of CP450 4A enzymes is shifted from EET production in NT rats toward inhibition of 20-HETE production in HT rats.

Original languageEnglish (US)
Pages (from-to)115-127
Number of pages13
JournalMicrocirculation
Volume8
Issue number2
DOIs
StatePublished - 2001

Keywords

  • 17-ODYA
  • 20-HETE
  • Arachidonic acid epoxidation
  • Arachidonic acid ω-hydroxylation
  • Cytochrome P450 4A enzymes
  • Hypoxia
  • Indomethacin
  • L-NAME
  • MS-PPOH
  • Vascular reactivity
  • Vascular smooth muscle

ASJC Scopus subject areas

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

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