5-Hydroxytryptamine- and U46619-mediated vasoconstriction in bovine pulmonary conventional and supernumerary arteries: effect of endogenous nitric oxide

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.