The effectiveness of alpha 2-adrenoceptor activation increases from the distal to the proximal part of the veins of canine limbs.

1. The effectiveness of alpha 1- and alpha 2-adrenoceptor activation was compared at different levels of the saphenous and cephalic vein of the dog in vitro. 2. Helically cut strips were used to determine concentration-response curves to phenylephrine, noradrenaline, UK-14,304 (5-bromo-6-(imidazoline-2-ylamino)-quinoxaline) and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetra-hydro-4H-(thiazo)-4,5-d-azepine). The effect of prazosin and yohimbine on these curves was also studied. 3. At the distal level, the maximum response to UK-14,304 amounted to 33 and 50% of those to noradrenaline in the saphenous and cephalic vein, respectively, while at the proximal level the maximum response to UK-14,304 amounted to 72 and 78% of those to noradrenaline, in the saphenous and cephalic vein, respectively. 4. In both vessels, the results obtained with B-HT 920 were very similar to those for UK-14,304. 5. The pD2 values for UK-14,304 - which were identical at the three levels of both vessels - and the pA2 values for the antagonism exerted by either prazosin or yohimbine against the responses to UK-14,304 indicate that the alpha 2-adrenoceptors are identical at the different levels of both vessels. 6. These results show that the effectiveness of alpha 2-adrenoceptor stimulation increases from the distal to the proximal regions of canine limb veins. Apparently, this is due to a greater density of alpha 2-adrenoceptors in the proximal regions. 7. Yohimbine is much more potent against phenylephrine distally than proximally in both vessels. However, after 30 nm phenoxybenzamine - a concentration which eliminates the vast majority of alpha,-adrenoceptors without affecting alpha 2-adrenoceptors - yohimbine became equally potent at both levels, suggesting that the difference existing before phenoxybenzamine depended on alpha,-adrenoceptors. Hence it is concluded that alpha,-adrenoceptors in distal and proximal portions may differ.