EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice

Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2462-9. doi: 10.1152/ajpheart.2001.280.6.H2462.

Abstract

Vasodilation to increases in flow was studied in isolated gracilis muscle arterioles of female endothelial nitric oxide synthase (eNOS)-knockout (KO) and female wild-type (WT) mice. Dilation to flow (0-10 microl/min) was similar in the two groups, yet calculated wall shear stress was significantly greater in arterioles of eNOS-KO than in arterioles of WT mice. Indomethacin, which inhibited flow-induced dilation in vessels of WT mice by approximately 40%, did not affect the responses of eNOS-KO mice, whereas miconazole and 6-(2-proparglyoxyphenyl)hexanoic acid (PPOH) abolished the responses. Basal release of epoxyeicosatrienonic acids from arterioles was inhibited by PPOH. Iberiotoxin eliminated flow-induced dilation in arterioles of eNOS-KO mice but had no effect on arterioles of WT mice. In WT mice, neither N(omega)-nitro-L-arginine methyl ester nor miconazole alone affected flow-induced dilation. Combination of both inhibitors inhibited the responses by approximately 50%. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) alone inhibited flow-induced dilation by approximately 49%. ODQ + indomethacin eliminated the responses. Thus, in arterioles of female WT mice, nitric oxide and prostaglandins mediate flow-induced dilation. When eNOS is inhibited, endothelium-derived hyperpolarizing factor substitutes for nitric oxide. In female eNOS-KO mice, metabolites of cytochrome P-450, via activation of large-conductance Ca2+-activated K+ channels of smooth muscle, mediate entirely the arteriolar dilation to flow.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives
  • 8,11,14-Eicosatrienoic Acid / metabolism
  • Animals
  • Arterioles / drug effects
  • Arterioles / metabolism*
  • Biological Factors / physiology*
  • Blood Flow Velocity / physiology
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • In Vitro Techniques
  • Large-Conductance Calcium-Activated Potassium Channels
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / blood supply*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / deficiency
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated*
  • Prostaglandins / metabolism
  • Prostaglandins / pharmacology
  • Stress, Mechanical
  • Vasodilation / drug effects
  • Vasodilation / physiology*

Substances

  • Biological Factors
  • Cyclooxygenase Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • Prostaglandins
  • endothelium-dependent hyperpolarization factor
  • Cytochrome P-450 Enzyme System
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • 8,11,14-Eicosatrienoic Acid