Influence of the endothelium and nitric oxide on the contractile responses evoked by 5-HT sub(1D) receptor agonists in the rabbit isolated saphenous vein

We investigated whether contractile responses evoked by 5-HT sub(1D) receptor agonists were influenced by the endothelium (E) and nitric oxide (NO) in the rabbit isolated saphenous vein. Saphenous vein rings were set up for isometric tension recording in oxygenated (5% CO sub(2) in O sub(2)) Krebs solution (pH 7.4) containing (10 super(-6) M): idazoxan (1), indomethacin (10), ketanserin (0.1), prazosin (10), and N super( omega ) nitro-L-arginine methyl ester (L-NAME; 0 or 10), a NO synthase inhibitor. In some experiments, the E was removed mechanically. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and sumatriptan (Sum) contracted rabbit saphenous vein rings in the potency order (pD sub(2) range) of 5-CT(7.2-7.6) > 5-HT(6.2-7.1) > Sum(5.0-5.8), irrespective of the presence or absence of the E or L-NAME (n = 9-37 per group) indicating that the potencies of the 3 agonists were not significantly affected by either the E or L-NAME. Efficacy, as assessed by the maximal contractile response (E sub(max)), was significantly greater for Sum compared to 5-HT and 5-CT with intact E irrespective of the presence (77 plus or minus 3, 62 plus or minus 3, and 50 plus or minus 3 mN respectively; P < 0.05 Sum versus 5-HT and 5-CT) or absence (26 plus or minus 3, 14 plus or minus 4, and 13 plus or minus 2 mN respectively; P < 0.05 Sum versus 5-HT and 5-CT) of L-NAME. In E-denuded rings, the E sub(max) values were all higher than in E-intact rings and did not differ between the 3 agonists (36 plus or minus 4, 37 plus or minus 4, and 36 plus or minus 5 mN for Sum, 5-HT and 5-CT, respectively; P > 0.5 between the 3 agonists) indicating that an endothelium-derived relaxing factor (EDRF) counteracted the constrictor activities of the 5-HT sub(1D) receptor agonists and raising the possibility that a component of the Sum-induced contractile responses was E-dependent. Without E, the presence of L-NAME did not significantly affect the E sub(max) values of the 3 agonists (41 plus or minus 4, 41 plus or minus 5, and 41 plus or minus 4 mN for Sum, 5-HT, and 5-CT respectively; P > 0.5 between the 3 agonists) indicating that the NO synthase inhibited was of endothelial origin. Potentiation of the E sub(max) of the 3 agonists by L-NAME was significantly albeit partially reversed by L-arginine (10 super(-2) M) indicating that NO synthase was indeed inhibited by L-NAME. Furthermore, in the presence of E, potentiation of E sub(max) of the 3 agonists by L-NAME was mimicked by meth