Effects of isoprenaline on contractile force and intracellular cyclic 3′,5′-nucleotide levels in the hypodynamic frog ventricle

Abstract

The increase in contractility which occurs in response to @-adrenergic stim~ation of the heart is thought to be mediated through changes in the levels of intracellular adenosine 3’,5’-cyclic monophosphate (cyclic AMP) [l-5] The possibility that guanosine 3’S’-cyclic monophosphate (cyclic GNP) is also involved in regulating the contractile response of the heart has received comparatively little attention. This is somewhat surprising since it has been shown that the negative inotropic response to acetylcholine is associated with a rise in intracelfular cyclic GMP [6--81, and that the levels of both cyclic AMP and cyclic GMP undergo oscillatory changes which are synchronised with the cardiac cycle [9]. In addition, we demonstrated that the development of the hypodynamic condition [lo] and the inotropic response of the isolated frog ventricle to stimulation with exogenous ATP [ 11 ,121 are characterized by changes in the levels of both cyclic 3’,5’-nucleotides. Moreover, in each instance a striking correlation exists between changes in isometric twitch tension and the ratio of (cyclic AMP}/(cyclic GMP). This paper presents results which show changes in the levels of cyclic AMP and cyclic GMP following stimulation of the hypodynamic frog ventricle with the P-agonist isoprenaline and here too there is a clear correlation between the magnitude of the contractile response and the change in the cyclic nucleotide ratio. 2. Methods Hearts from frogs, Rana ~ernp~ra~a and Rana esculenta, were isolated and superfused at room