Nitric-oxide-related and non-related mechanisms in the acetylcholine-evoked relaxations in cat femoral arteries.

The possible contribution of nitric oxide (NO) and other endothelial factors to the vasodilatation induced by acetylcholine (ACh) was analyzed in cat femoral arteries. For this purpose, the modifications by different treatments of ACh-induced relaxations were compared with those of exogenous NO-induced relaxations. Although the ACh-induced endothelium-dependent relaxation was not affected by the cyclooxygenase inhibitor indomethacin, it was partially inhibited by the lipoxygenase blocker 5,8,11,14-eicosatetraenoic acid, and by the NO inactivators phenidone, hydroquinone and oxyhemoglobin (OxHb). Additionally, this type of relaxation was reduced by the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) and abolished by NG-nitro-L-arginine methyl ester; these later effects were selectively antagonized by L-arginine. Exogenous NO-induced vasodilatations were abolished by OxHb and unmodified by L-NMMA. Blocking sodium pump activity decreased vasodilatations to ACh, NO, sodium nitroprusside and 8-bromoguanosine 3',5'-cyclic monophosphate. 4-Aminopyridine, a K+ channel antagonist, reduced the relaxation induced by ACh but not that induced by exogenous NO. These results suggest: (1) ACh-induced relaxation in these vessels is mainly due to endothelial cell NO release; (2) NO does not act on 4-AP-sensitive K+ channels, although these channels may be involved in NO release from the endothelium, and (3) one of the relaxant mechanisms of NO could be the activation of the vascular sodium pump.