8-Bromo cyclic GMP mimics the actions of nitroglycerin in modulating responses produced by full and partial alpha-adrenoceptor agonists in canine saphenous vein.

The purpose of the present study was to determine whether 8-bromo cyclic GMP (8-Br cGMP) mimics the actions of nitroglycerin (GTN) in inhibiting alpha-1 versus alpha-2 adrenoceptor-mediated constrictor responses in canine saphenous vein. Phenylephrine (PE) and L-dobutamine were used as full and partial alpha-1 adrenoceptor agonists, respectively, and B-HT 920 was employed as a selective alpha-2 adrenoceptor agonist. The ability of 8-Br cGMP and GTN to inhibit vasoconstrictor responses to a standard agonist concentration of PE, L-dobutamine and B-HT 920 was determined. 8-Br cGMP like GTN produced a selective antagonism of alpha-2-mediated responses of B-HT 920 and had minimal effects on alpha-1-induced constrictor responses of phenylephrine. However, when a portion of the alpha-1-adrenoceptor pool was inactivated by phenoxybenzamine (POB) (5 x 10(-8) M, 1 x 10(-7) M) 8-Br cGMP like GTN produced a significant depression of responses to PE. In addition, contractions produced by L-dobutamine, a selective partial alpha-1 adrenoceptor agonist (no alpha receptor reserve), were highly sensitive to inhibition by 8-Br cGMP and GTN. These results suggest that the presence of a large alpha-1-adrenoceptor reserve to PE concealed an underlying functional antagonism to alpha-1-adrenoceptor-mediated responses by GTN and 8-Br cGMP. The similarity in the efficacy and potency of these two agents (8-Br cGMP and GTN) suggests that the effects of GTN in canine saphenous vein may be the result of an increase in the intracellular concentration of cGMP.