Opposing regulatory influences of cyclic guanosine monophosphate and cyclic adenosine monophosphate in the control of cardiac muscle contraction.

The effects of acetylcholine chloride (ACh) and isoproterenol (Iso) on myocardial levels of guanosine 3', 5'-monophosphate (cyclic GMP) and adenosine 3', 5'-monophosphate (cyclic AMP) and on force of contraction were studied in elelctrically driven isolated rabbit atria. Incubation of atria with Tyrode's solution containing ACh (5 x 10(-7) M) produced significant decreases in contractile force that were associated with significant elevations in atrial cyclic GMP levels. Atrial levels of cyclic AMP were significantly lowered at 15 sec after the addition of ACh but were only slightly lowered at earlier time intervals. The effects of acetylcholine on force of contraction and on cyclic nucleotide levels were prevented with atropine (1 x 10(-7) M). The addition of Iso (1 x 10(-7)-M) to isolated atria produced significant increases in contractile force that were associated with significant elevations in effects of Iso on force of contraction and on cyclic nucleotide levels were prevented with practolol (1 x 10(-5) M). The increases in atrial cyclic GMP and cyclic AMP levels following addition of ACh and Iso, respectively, precede the changes in contractile force. These data support our hypothesis that cyclic AMP and cyclic GMP exert oppositional effects on cardiac contrctility.