5-Hydroxytryptamine- and U466 19-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 est er (L-NAME) (100 mu M) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadia zolo[4,3-a]quinoxalin-1-one (ODQ) (10 mu M) on the responses of CA and SA t o 5-HT and U46619 were also examined. In addition, the effects of the 5-HT2 B receptor antagonist SE 200646 (1 nM-1 mu M) on the responses to 5-HT in S A and CA were studied. Tissue cGMP levels were measured in the absence and presence of L-NAM E, ODQ, 5-HT and U46619. 5-HT was approximately 30 times more potent in SA {- log [EC50 (M)] (pEC(50)) 6.32 +/- 0.13} than in CA (5. 05 +/- .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 rest ing 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-NAM E nor ODQ altered the respon ses to U466 19 in SA, but both L-NAME and ODQ increased the magnitude of th e response to 5-HT in SA without changing the sensitivity. Inhibition of th e 5-MT,, receptor with SE 200646 did not alter the response to 5-HT in SA o r 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 pr esence of 5-HT or U46619. L-NAME and ODQ reduced the basal levels of cGMP i n both SA and CA. The results suggest that endogenous NO selectively attenu ates the vasoconstrictor response to 5-HT in SA, but not in CA. These resul ts 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 ab sence of this pathway.