title: Enhanced release of prostaglandins contributes to flow-induced arteriolar dilation in eNOS knockout mice.
abstract: Nitric oxide and prostaglandins were shown to contribute to the endothelial mediation of flow-induced dilation of skeletal muscle arterioles of rats. Thus, we hypothesized that flow-induced dilation and its mediation are altered in gracilis muscle arterioles of mice deficient in the gene for endothelial nitric oxide synthase (eNOS-KO) compared with control wild-type (WT) mice. Gracilis muscle arterioles ( approximately 80 micrometer) of male mice were isolated, then cannulated and pressurized in a vessel chamber. The increases in diameter elicited by increases in perfusate flow from 0 to 10 microq/min were similar in arterioles from eNOS-KO (n=28) and WT (n=22) mice ( approximately 20 micrometer at 10 microL/min flow). Removal of the endothelium eliminated flow-induced dilations in vessels of both strains of mice. N(omega)-nitro-L-arginine (L-NNA, 10(-4) mol/L) significantly inhibited flow-induced dilation in arterioles of WT mice by approximately 51% but had no effect on responses of arterioles from eNOS-KO mice. Indomethacin (INDO, 10(-5) mol/L) inhibited flow-induced dilation of WT mice by approximately 49%, whereas it completely abolished this response in arterioles of eNOS-KO mice. Simultaneous administration of INDO and L-NNA eliminated flow-induced responses in arterioles of WT mice. Dilations to carbaprostacyclin were similar at concentrations of 10(-8) and 3x10(-8) mol/L but decreased significantly at 10(-7) mol/L in arterioles of eNOS-KO compared with those of WT mice. These findings demonstrate that, despite the lack of nitric oxide mediation, flow-induced dilation is close to normal in arterioles of eNOS-KO mice because of an enhanced release of endothelial dilator prostaglandins and suggest that this vascular adaptation may contribute to the regulation of peripheral resistance in eNOS-KO mice.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Huang
authors.forename: C J
authors.initials: CJ
authors.lastname: Smith
authors.forename: C J
authors.initials: CJ
authors.lastname: Stackpole
authors.forename: J A
authors.initials: JA
authors.lastname: Connetta
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: D000818:Animals; D001160:Arterioles / Q000502:physiology*; D001775:Blood Circulation / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D019335:Nitroarginine; C026678:carboprostacyclin; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D007213:Indomethacin