title: Increased contribution of L-arginine-nitric oxide pathway in aorta of mice lacking the gene for vimentin.
abstract: Experiments were designed to investigate endothelial function in the aorta of mice lacking the gene for the cytoskeleton protein vimentin (vim -/- ). Rings with and without endothelium from wild-type (vim +/+ ), heterozygous (vim +/- ), and homozygous (vim -/- ) mice were suspended in organ chambers to record of changes in isometric tension. During phenylephrine contraction, acetylcholine evoked comparable endothelium-dependent relaxations in the three groups. In the presence of Nomega-nitro-L-arginine, acetylcholine caused endothelium-dependent contractions, which were greater in vim -/- than in vim +/+ and vim +/- aortas. Indomethacin did not affect relaxation to acetylcholine in vim +/+ or in vim +/-, but it significantly increased the maximal response in vim -/- (67 +/- 7 vs. 102 +/- 4%). Response to acetylcholine in vim -/- aortas was not affected by cyclooxygenase type 2 inhibitor NS-398, the thromboxane receptor antagonist SQ-29,548, or superoxide dismutase. Relaxations to sodium nitroprusside were not different between vim +/+ and vim -/- mice and were not affected by cyclooxygenase inhibition. Cyclic guanosine monophosphate levels, which were increased to a comparable level by acetylcholine in vim +/+ and vim -/-, were augmented by indomethacin in vim -/- aortas but not in vim +/+ aortas. Expression of endothelial nitric oxide synthase was not different between vim +/+ and vim -/- preparations. These results suggest that despite comparable endothelium-dependent responses to acetylcholine, endothelial cells from vim -/- mice release a cyclooxygenase product that compensates the augmented contribution of nitric oxide.
authors.affiliation: INSERM Unit 541, Vascular Biology, Hôpital Lariboisiére, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Henrion
authors.forename: T
authors.initials: T
authors.lastname: Ebrahimian
authors.forename: J
authors.initials: J
authors.lastname: Benessiano
authors.forename: E
authors.initials: E
authors.lastname: Colucci-Guyon
authors.forename: F
authors.initials: F
authors.lastname: Langa
authors.forename: B I
authors.initials: BI
authors.lastname: Lévy
authors.forename: C M
authors.initials: CM
authors.lastname: Boulanger
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001120:Arginine / Q000502:physiology*; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology; D014746:Vimentin / Q000172:deficiency* / Q000235:genetics*
chemical_list: D014665:Vasodilator Agents; D014746:Vimentin; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine