title: 5-hydroxytryptamine- and U46619-mediated vasoconstriction in bovine pulmonary conventional and supernumerary arteries: effect of endogenous nitric oxide.
abstract: We compared 5-hydroxytryptamine (5-HT)- and U46619-mediated contractions in bovine pulmonary conventional arteries (CA) and supernumerary arteries (SA). The effects of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (100 microM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ) (10 microM) on the responses of CA and SA to 5-HT and U46619 were also examined. In addition, the effects of the 5-HT(2B) receptor antagonist SB 200646 (1 nM-1 microM) on the responses to 5-HT in SA and CA were studied. Tissue cGMP levels were measured in the absence and presence of L-NAME, ODQ, 5-HT and U46619. 5-HT was approximately 30 times more potent in SA ¿-log[EC(50) (M)] (pEC(50)) 6.32+/-0.13¿ than in CA (5.05+/-0.14). U46619 displayed a similar potency in both CA (pEC(50) 7.80+/-0.07) and SA (7.75+/-0. 12). L-NAME did not significantly alter the resting tone of CA or SA. In contrast, ODQ produced a transient increase in the tone of both CA and SA. Neither L-NAME nor ODQ altered the responses to 5-HT or U46619 in CA. In addition, neither L-NAME nor ODQ altered the responses to U46619 in SA, but both L-NAME and ODQ increased the magnitude of the response to 5-HT in SA without changing the sensitivity. Inhibition of the 5-HT(2B) receptor with SB 200646 did not alter the response to 5-HT in SA or CA. Basal levels of cGMP (pmol/mg of protein) were similar in CA (1.16+/-0.33) and SA (0. 8+/-0.51), and were not significantly changed in the presence of 5-HT or U46619. L-NAME and ODQ reduced the basal levels of cGMP in both SA and CA. The results suggest that endogenous NO selectively attenuates the vasoconstrictor response to 5-HT in SA, but not in CA. These results also suggest that the NO/cGMP pathway may have a role in maintaining low vascular tone, but that other mechanisms are able to compensate for the absence of this pathway.
authors.affiliation: School of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Rd., Glasgow G4 0BA, Scotland, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Bunton
authors.forename: A
authors.initials: A
authors.lastname: MacDonald
authors.forename: T
authors.initials: T
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Tracey
authors.forename: J C
authors.initials: JC
authors.lastname: McGrath
authors.forename: A M
authors.initials: AM
authors.lastname: Shaw
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D007211:Indoles; D010069:Oxadiazoles; D011810:Quinoxalines; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D009569:Nitric Oxide; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D014508:Urea; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester