Infirmary, Bristol BS2 8HW1 The NO donor 3-morpholino-sydnonimine (SIN-1; 0.01-1O UM) evoked concentration-dependent relaxation of rat isolated mesenteric arteries pre-constricted with phenylephrine (1-3 uM). The relaxation to SIN-i 5 Exposure of intact arterial segments to charybdotoxin and apamin, in the presence of NO synthase blockers, also significantly inhibited SIN-i-evoked relaxation, reducing the maximum response by around 80% (n=4; P<0.01). 6 Addition of superoxide dismutase (SOD; 30 u ml-1), potentiated relaxations to SIN-i in all tissues, but did not alter the effects of charybdotoxin and ODQ on SIN-i-evoked relaxation. 7 These data show that although relaxation to the NO-donor SIN-1 is not significantly different between endothelium-intact and denuded arterial segments, the mechanisms which mediate SIN-1-evoked relaxation in the rat isolated mesenteric artery appear to be modulated by the basal release of endothelium-derived NO. In the presence of an intact endothelial cell layer, the major mechanism for SIN-i-evoked relaxation appears to be the activation of charybdotoxin-sensitive potassium channels. In contrast, when basal NO synthesis is inhibited, SIN-1 appears to cause full relaxation by both the activation of a charybdotoxin-sensitive pathway and the stimulation of soluble guanylyl cyclase.