Experiments were designed to determine the effect of cooling on alpha-1 and alpha-2 adrenergic responses in isolated canine veins. Rings 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°C) augmented contractions to norepinephrine in saphenous but caused depression in femoral veins. Cooling (to 24° 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. The alpha-2 adrenergic response is so inefficient in this blood vessel that an increase in alpha-2 adrenoceptor affinity cannot overcome the inhibitory effect of cooling. Therefore, in the femoral vein, cooling inhibits alpha-1 and alpha-2 adrenergic responses and, thus, depresses responses produced by norepinephrine.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1986|
ASJC Scopus subject areas
- Molecular Medicine