Characterization of postjunctional alpha-1 and alpha-2 adrenoceptors activated by exogenous or nerve-released norepinephrine in the canine saphenous vein

Abstract

Experiments were designed to characterize alpha-1 and alpha-2 adrenoceptor-mediated effects in the canine saphenous vein. Rings of saphenous vein were mounted for isometric tension recording in physiological saline solution. Contractile responses evoked by alpha-1 adrenoceptor agonists, cirazoline or St 587 were inhibited by alpha-1 antagonists, prazosin (pA2 = 7.9) or phenoxybenzamine, but were relatively resistant to the alpha-2 adrenoceptor antagonist rauwolscine. The responses to alpha-2 adrenoceptor agonists, xylazine or B-HT 920, were relatively resistant to prazosin or phenoxybenzamine but were antagonized by rauwolscine (pA2 = 8.7). After phenoxybenzamine, the alpha-2 agonists, M-7, guanfacine, UK 14304, B-HT 920 and xylazine evoked similar maximal increases in tension which were considerably smaller (approximately 50%) than that attained by alpha-1 adrenoceptor stimulation. The different concentration effect characteristics of these responses were also revealed using norepinephrine. Prazosin produced a biphasic effect on the concentration-response curve of norepinephrine, being more potent against responses above 50% of the maximum (pA2 = 7.9) compared to lower increases in tension (pA2 = 6.2). After alpha-1 adrenoceptor blockade with prazosin, rauwolscine was more effective against responses below 50% of the maximum, compared to higher increases in tension. The results suggest that the alpha-1 and alpha-2 adrenoceptor-mediated concentration-effect curves to norepinephrine are almost coincident and that alpha-2 adrenergic stimulation produces only partial activation of the vascular smooth muscle. Contractile responses produced by sympathetic nerve stimulation or by tyramine were antagonized more effectively by the combination of prazosin plus rauwolscine than by either blocker given alone, suggesting that alpha-1 and alpha-2 adrenoceptors are both innervated by sympathetic nerves in the canine saphenous vein.