EFFECTS OF FORSKOLIN, TREQUINSINE AND ISOPROTERENOL ON NOREPINEPHRINE–INDUCED CONTRACTIONS, cAMP AND cGMP LEVELS OF ISOLATED VASCULAR TISSUE

SUMMARY Forskolin (FOR), a direct stimulator of adenylate cyclase, trequinsine (TRE), a phosphodiesterase-inhibitor, and isoproterenol (ISO), a s-receptor agonist were used to elucidate the relationship between vascular responses and cyclic nucleotide levels in isolated rabbit aortic tissue. All agents reduced norepinephrine (NE)-vasoconstrictive responses in a dose dependent manner with IC 50 values of 4.1×10-8M, 8.5×10 -7 M and 4.0×10 -7 M, respectively, accompanied by increases of cAMP and cGMP (measured with RIA). All three agents attenuated acetylcholine (ACh)-induced relaxations of aortic rings in a dose dependent manner. High concentrations of FOR (10 -7 M) and TRE (10 -5 M) even reversed ACh-induced relaxations, comparable to ACh effects in de-endothelialized vascular tissue. It is suggested that FOR, TRE and ISO-induced relaxations of isolated rabbit aortic preparations, accompanied by increases in cAMP and cGMP, interact with endothelium-derived relaxing-factor (EDRF) dependent relaxations.