The actions of medetomidine may not be mediated exclusively by alpha(2)-adrenoceptors in the equine saphenous vein

Spirals of endothelially denuded equine saphenous vein were used to study the pre- and post-junctional effects of medetomidine in vitro. The pD(2) values were calculated for noradrenaline (6.7 +/- 0.1), phenylephrine (5.6 +/- 0.1), BHT 920 (6.2 +/- 0.2) and UK 14304 (5.7 +/- 0.2), Medetomidine produced a biphasic response, with a pD(2)1 of 8.2 +/- 0.1 and a pD(2)2 of 5.7 +/- 0.1 in the equine saphenous vein (n = 6). Prazosin (10(-7) M) significantly shifted the second phase of the medetomidine concentration-response curve to the right (pD(2)1 was 8.1 +/- 0.2 and pD(2)2 was 5.0 +/- 0.2, P < 0.05). Rings of equine saphenous vein were electrically stimulated to investigate the pre-junctional effects of medetomidine. Increasing concentrations of the alpha(2)-adrenoceptor agonist BHT 920 reduced the response to electrical stimulation in a concentration dependent manner to a maximum of 40 +/- 5%, whereas medetomidine (0.1-100 nM) caused a concentration dependent enhancement to a maximum of 490 +/- 150%. These results suggest alpha(1)- and alpha(2)-adrenoceptors are functional in the equine saphenous vein, but that medetomidine is not acting exclusively as an alpha(2)-adrenoceptor agonist.