Endothelium‐dependent contractile responses to 5‐hydroxytryptamine in the rabbit basilar artery

1 5‐Hydroxytryptamine (5‐HT) and 5‐carboxamidotryptamine (5‐CT) stimulated additional, endothelium‐dependent contractions in rabbit isolated basilar arteries which had been submaximally contracted with either histamine or potassium chloride. 2 The additional contractions to 5‐HT were not altered by the 5‐HT2 antagonist, ketanserin (1 μm), but were abolished in the presence of the cyclo‐oxygenase inhibitor indomethacin (3 μm). 3 The additional smooth muscle contraction stimulated by 5‐HT was increased in the presence of the competitive substrate inhibitor for nitric oxide synthase, NG‐nitro‐l‐arginine methyl ester (l‐NAME, 100 μm). 4 Neither of the selective 5‐HT agonists, 8‐hydroxy‐dipropylaminotetralin (8‐OH DPAT) or α‐methyl 5‐HT stimulated endothelium‐dependent contraction, but these agonists did reduce the rate at which histamine‐induced tension spontaneously declined. This effect represented a direct action on the smooth muscle cells, as it was independent of the presence of endothelial cells. 5 Smooth muscle relaxation was not obtained in response to 5‐HT, whether or not indomethacin was present to block endothelium‐dependent contraction. None of the other selective 5‐HT agonists, 5‐CT, 8‐OH DPAT or α‐methyl 5‐HT produced endothelium‐dependent smooth muscle relaxation, when applied against a background of contraction. 6 These data show that endothelium‐dependent smooth muscle contraction can be produced by stimulating 5‐HT receptors in the partially contracted rabbit basilar artery. Similar contraction to 5‐CT indicates an involvement by 5‐HT1 receptors. The susceptibility of the contractions to indomethacin suggest they are mediated by a metabolite of arachidonic acid.