Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

This study determined the contribution of cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid in mediating the constriction of isolated rat skeletal muscle resistance arteries in response to elevated PO2. Gracilis arteries (GA) were viewed via television microscopy and constrictor responses to elevated PO2 were measured with a video micrometer. Endothelium removal and treatment of GA with 17-octadecynoic acid (17-ODYA; suicide substrate inhibitor of CP450 4A enzymes) impaired oxygen-induced constriction of the vessels; treatment of endothelium-denuded GA with 17-ODYA eliminated responses to elevated PO2. NOS inhibition and inhibition of EET production had no effect on oxygen-induced constriction of the vessels, although cyclooxygenase inhibition with indomethacin impaired GA responses to elevated PO2. Treatment of GA with dibromododecenyl methylsulfimide (DDMS; inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) production) or 6(Z),15(Z)-20-HEDE (antagonist for 20-HETE receptors) mimicked the effects of 17-ODYA on GA responses to elevated PO2. Treatment of vessels with iberiotoxin or glibenclamide reduced the constriction of the vessels in response to elevated PO2 while treatment with both K+ channel blockers eliminated oxygen-induced constriction of the vessels. Following treatment of GA with indomethacin and 20-HETE, the vessels failed to respond to elevated PO2. These results suggest that oxygen-induced constriction of skeletal muscle resistance arteries represents the combined effects of reduced prostanoid release from the vascular endothelium and enhanced 20-HETE production in vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)271-283
Number of pages13
JournalMicrovascular Research
Volume62
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Constriction
Prostaglandins
Muscle
Skeletal Muscle
Arteries
Oxygen
Indomethacin
Cytochrome P-450 Enzyme System
Glyburide
Enzymes
Prostaglandin-Endoperoxide Synthases
Metabolites
Television
Arachidonic Acid
Rats
Microscopic examination
Endothelium
Cells
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Substrates

Keywords

  • 20-HETE
  • 20-hydroxyeicosatetraenoic acid
  • Arachidonic acid metabolism
  • Cytochrome P450 4A enzymes
  • EET
  • Epoxyeicosatrienoic acid
  • K channels
  • K channels
  • Microcirculation
  • Oxygen
  • Potassium channels
  • Vascular reactivity
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

Cite this

Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries. / Frisbee, Jefferson C.; Krishna, U. Murali; Falck, J R; Lombard, Julian H.

In: Microvascular Research, Vol. 62, No. 3, 2001, p. 271-283.

Research output: Contribution to journalArticle

Frisbee, Jefferson C. ; Krishna, U. Murali ; Falck, J R ; Lombard, Julian H. / Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries. In: Microvascular Research. 2001 ; Vol. 62, No. 3. pp. 271-283.
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AU - Lombard, Julian H.

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AB - This study determined the contribution of cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid in mediating the constriction of isolated rat skeletal muscle resistance arteries in response to elevated PO2. Gracilis arteries (GA) were viewed via television microscopy and constrictor responses to elevated PO2 were measured with a video micrometer. Endothelium removal and treatment of GA with 17-octadecynoic acid (17-ODYA; suicide substrate inhibitor of CP450 4A enzymes) impaired oxygen-induced constriction of the vessels; treatment of endothelium-denuded GA with 17-ODYA eliminated responses to elevated PO2. NOS inhibition and inhibition of EET production had no effect on oxygen-induced constriction of the vessels, although cyclooxygenase inhibition with indomethacin impaired GA responses to elevated PO2. Treatment of GA with dibromododecenyl methylsulfimide (DDMS; inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) production) or 6(Z),15(Z)-20-HEDE (antagonist for 20-HETE receptors) mimicked the effects of 17-ODYA on GA responses to elevated PO2. Treatment of vessels with iberiotoxin or glibenclamide reduced the constriction of the vessels in response to elevated PO2 while treatment with both K+ channel blockers eliminated oxygen-induced constriction of the vessels. Following treatment of GA with indomethacin and 20-HETE, the vessels failed to respond to elevated PO2. These results suggest that oxygen-induced constriction of skeletal muscle resistance arteries represents the combined effects of reduced prostanoid release from the vascular endothelium and enhanced 20-HETE production in vascular smooth muscle cells.

KW - 20-HETE

KW - 20-hydroxyeicosatetraenoic acid

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KW - Epoxyeicosatrienoic acid

KW - K channels

KW - K channels

KW - Microcirculation

KW - Oxygen

KW - Potassium channels

KW - Vascular reactivity

KW - Vascular smooth muscle

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DO - 10.1006/mvre.2001.2341

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JO - Microvascular Research

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