RT Journal Article SR Electronic T1 Effect of cooling on alpha-1 and alpha-2 adrenergic responses in canine saphenous and femoral veins. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 139 OP 147 VO 238 IS 1 A1 N A Flavahan A1 P M Vanhoutte YR 1986 UL http://jpet.aspetjournals.org/content/238/1/139.abstract AB Experiments were designed to determine the effects of cooling on alpha-1 and alpha-2 adrenergic responses in isolated canine veins. Rings of saphenous and femoral veins were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution, gassed with 95% O2 and 5% CO2. Cooling (from 37-24 degrees C) augmented contractions to norepinephrine in saphenous but caused depression in femoral veins. Cooling (to 24 degrees C) had no effect on alpha-1 adrenergic responses evoked by phenylephrine in saphenous veins but caused depression in femoral veins. Alpha-2 adrenergic responses produced by UK 14,304 were augmented by cooling in the saphenous but were virtually abolished by cooling in femoral veins. Cooling decreased the dissociation constant (i.e., increased affinity) of corynanthine for alpha-1 adrenoceptors in saphenous and femoral veins (approximately 3-fold), and the dissociation constant of rauwolscine for alpha-2 adrenoceptors in saphenous veins (approximately 7.5-fold). The influence of cooling on alpha adrenoceptor responsiveness was analyzed using computer-generated receptor-models. The results suggest that the differential sensitivity of cutaneous and deep blood vessels to cooling results from differences in efficiency of alpha-1 and alpha-2 adrenoceptor response coupling. In the saphenous vein, there is a large alpha-1 adrenoceptor reserve which buffers the alpha-1 adrenergic response from the inhibitory influence of cooling. This coupled with a cooling-induced increase in alpha-2 adrenoceptor affinity ensures that cooling augments the response to norepinephrine. In the femoral vein, there is no alpha-1 adrenoceptor reserve and cooling therefore depresses alpha-1 adrenergic responses.(ABSTRACT TRUNCATED AT 250 WORDS)