title: Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice.
abstract: Previous studies have demonstrated that responses to endothelium-dependent vasodilators are absent in the aortas from mice deficient in expression of endothelial nitric oxide synthase (eNOS -/- mice), whereas responses in the cerebral microcirculation are preserved. We tested the hypothesis that in the absence of eNOS, other vasodilator pathways compensate to preserve endothelium-dependent relaxation in the coronary circulation. Diameters of isolated, pressurized coronary arteries from eNOS -/-, eNOS heterozygous (+/-), and wild-type mice (eNOS +/+ and C57BL/6J) were measured by video microscopy. ACh (an endothelium-dependent agonist) produced vasodilation in wild-type mice. This response was normal in eNOS +/- mice and was largely preserved in eNOS -/- mice. Responses to nitroprusside were also similar in arteries from eNOS +/+, eNOS +/-, and eNOS -/- mice. Dilation to ACh was inhibited by N(G)-nitro-L-arginine, an inhibitor of NOS in control and eNOS -/- mice. In contrast, trifluoromethylphenylimidazole, an inhibitor of neuronal NOS (nNOS), decreased ACh-induced dilation in arteries from eNOS-deficient mice but had no effect on responses in wild-type mice. Indomethacin, an inhibitor of cyclooxygenase, decreased vasodilation to ACh in eNOS-deficient, but not wild-type, mice. Thus, in the absence of eNOS, dilation of coronary arteries to ACh is preserved by other vasodilator mechanisms.
authors.affiliation: Departments of Internal Medicine and Pharmacology, The Cardiovascular Center, University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA. klamping@blue.weeg.uiowa.edu
authors.forename: K G
authors.initials: KG
authors.lastname: Lamping
authors.forename: D W
authors.initials: DW
authors.lastname: Nuno
authors.forename: E G
authors.initials: EG
authors.lastname: Shesely
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: F M
authors.initials: FM
authors.lastname: Faraci
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011109:Polymethacrylic Acids / Q000494:pharmacology; D012016:Reference Values; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D011109:Polymethacrylic Acids; D014665:Vasodilator Agents; C091347:vinyl ethyl methacrylate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine; D007213:Indomethacin