Involvement of nitric oxide in fading of 5-hydroxytryptamine-induced vasocontraction

This investigation was done to determine whether vascular nitric oxide is involved in the fading of 5-hydroxytryptamine (5-HT)-induced contraction of isolated aortic strips from rats. The 5-HT (100 microM)-induced contractile response showed a gradual decrease in tension after a plateau level had been attained. The degree of the fadeaway was less in strips without endothelium than in those with endothelium. Pretreatment with nitro-L-arginine (100 microM) or haemoglobin (10 microM) suppressed the fadeaway of 5-HT contraction in both types of strips, although the effect was less in strips without endothelium. In contrast to 5-HT contraction, phenylephrine (10 microM) contraction in the presence of endothelium did not begin fading away for at least 1 hr after stimulation. In strips precontracted with 5-HT (100 microM), relaxation induced by sodium nitroprusside (1-50 nM) was significantly higher than in those precontracted with phenylephrine (10 microM). There was no significant difference between the cyclic GMP levels at 1 hr after stimulation with phenylephrine (10 microM) and 5-HT (100 microM). These results suggest that decrease in vascular tone in rat aorta after the plateau of 5-HT contraction has been reached is in part due to nitric oxide derived from vascular endothelial and non-endothelial cells. The vascular tone decreases more quickly after the plateau in the case of 5-HT contraction than of phenylephrine contraction, which may be due to higher sensitivity of 5-HT contraction to nitric oxide.