Relaxation response of isolated canine veins to agents that act on the adenylate cyclase-cyclic AMP system: further investigation.

The present study was undertaken to clarify whether there is a deficiency in the relaxation mediated by the adenylate cyclase-cyclic AMP (cAMP) system in the portal vein as compared to the saphenous vein. Longitudinal strips of the portal vein and helical preparations of the saphenous vein were used. The relaxation response to various agents was examined under conditions such that the venous preparations were previously contracted by methoxamine in equipotent concentrations (EC80), i.e., 10(-6) M for portal vein and 10(-5) M for saphenous vein. The saphenous vein relaxed fully in response to isoproterenol but the portal vein relaxed only to 29% of the maximum relaxation induced by papaverine 10(-4) M. However, dibutyryl cAMP and 8-bromo-cAMP, membrane permeable derivatives of cAMP, 3-isobutyl-1-methylxanthine and papaverine, phosphodiesterase inhibitors, and forskolin, a direct stimulator of adenylate cyclase, relaxed portal and saphenous veins similarly though with quantitative differences. The results suggest that there is no profound deficiency in the adenylate cyclase-cAMP system but there may be a deficiency in the coupling between surface beta-adrenoceptors and adenylate cyclase or there may be a low density of beta-adrenoceptors in the portal vein.