Levels of Cyclic AMP and Electrical Events during Inhibition of Contractile Activity in Vascular Smooth Muscle

The possible relationship between changes in electrical and mechanical activity and in tissue levels of cyclic AMP (cAMP) during relaxation of the myogenical active rat portal vein has been elucidated in response to different inhibitory stimuli. Isoproterenol, 10(-5) M, caused an initial pronounced inhibition of spike discharge and contractions followed by a partial recover over the 15 min exposure period. This inhibitory response was associated with doubling of tissue cAMP after 1 min and a less pronounced increase in later measurements (5 and 15 min). Papaverine, 10(-4)M, caused, in contrast, an inhibition of electrical and mechanical activity which developed gradually over the entire 15 min exposure period. The levels of cAMP at 1,5 and 15 min all exceeded the corresponding values obtained with isoproterenol. The two drugs in combination gave a biphasic inhibitory response associated with a sustained large increase in the level of cAMP. These drug induced inhibitions were thus accompanied by increased levels of cAMP, but the different time courses of the electromechanical responses could not be rlated to corresponding variations in the content of cAMP. Hyperosmolality (+150 mM sucrose) and mechanical vibration (100 Hz) elicited differentiated inhibitions of smooth muscle activity without changes in tissue cAMP. The mechanical effects elicited by isoproterenol, papaverine and hyperosmolality were accompanied by approximately parallel changes in electrical spike discharge. It is concluded that increased levels of cAMP are not indispensible for vascular smooth muscle relaxation, and that the magnitude of pharmacologically induced inhibitions are not always closely related to the total tissue content of the nucleotide.