title: EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice.
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.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: A
authors.initials: A
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: M A
authors.initials: MA
authors.lastname: Carroll
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: C J
authors.initials: CJ
authors.lastname: Smith
authors.forename: J A
authors.initials: JA
authors.lastname: Connetta
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
authors.forename: E G
authors.initials: EG
authors.lastname: Shesely
authors.forename: A
authors.initials: A
authors.lastname: Koller
authors.forename: G
authors.initials: G
authors.lastname: Kaley
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D001685:Biological Factors / Q000502:physiology*; D001783:Blood Flow Velocity / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D013314:Stress, Mechanical; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D003577:Cytochrome P-450 Enzyme System; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D015126:8,11,14-Eicosatrienoic Acid