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 NG-nitro-l-arginine methyl ester (l-NAME) (100 μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 μM) on the responses of CA and SA to 5-HT and U46619 were also examined. In addition, the effects of the 5-HT2B receptor antagonist SB 200646 (1 nM–1 μM) 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 [EC50 (M)] (pEC50) 6.32±0.13} than in CA (5.05±0.14). U46619 displayed a similar potency in both CA (pEC50 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-HT2B 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.

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