INFLUENCE OF SPACEFLIGHT, HINDLIMB SUSPENSION, AND VENOUS OCCLUSION ON ALPHA(1)-ADRENOCEPTORS IN RAT VENA-CAVA

Effects of hindlimb suspension, spaceflight, and venous occlusion were examined in isolated strips from rat vena cava by using both [H-3]prazosin-binding and contraction responses evoked by norepinephrine. Sensitivity to norepinephrine was decreased without modification of the maximal contractile response. Furthermore, the high K+-induced contractions were not affected, suggesting that there was no interference with voltage-dependent Ca2+ channels. The sensitivity of the norepinephrine-induced contraction to prazosin was decreased, and Scatchard analysis of [H-3] prazosin binding indicated an increase in the dissociation constant without variation in maximal binding capacity. A similar increase in the dissociation constant was obtained in control rats after pretreatment with 3 mu M norepinephrine or 0.1 mu M phorbol 12,13-dibutyrate to desensitize the protein kinase C. This effect was completely abolished in the presence of GF-109203X, a selective inhibitor of protein kinase C. Taken together, these data indicate that altered gravity conditions induce a desensitization of alpha(1B)-adrenoceptors depending on increased protein kinase C activity. This effect can be mimicked by venous occlusion and may be responsible for reduced contractile responses to norepinephrine.