Evidence for opposing influences of cyclic GMP and cyclic AMP on force of contraction in mammalian myocardium.

The inotropic effects of the 8-Br-derivatives of cyclic GMP and cyclic AMP were investigated in guinea pig or rat auricles and papillary muscles from cats. In guinea pig auricles, 8-Br-cyclic GMP had a concentration-dependent negative inotropic effect, whereas 8-Br-cyclic AMP had a concentration-dependent positive inotropic effect. A negative inotropic effect of 8-Br-cyclic GMP in rat auricles was obtained with 30 times lower doses than in guinea pig auricles; the pacemaker activity of spontaneously beating rat right auricles did not change in response to 8-Br-cyclic GMP. In cat papillary muscles, 8-Br-cyclic GMP (3 X 10(-4) M) also produced a negative inotropic effect. In contrast, 8-Br-cyclic AMP (3 X 10(-4) M) did not affect force of contraction; however, after pretreatment with the strong phosphodiesterase inhibitor papaverine (2 X 10(-5) M) 8-Br-cyclic AMP (3 X 10(-4) M) had a strong positive inotropic effect also in cat papillary muscles. The results suggest opposite influences of cyclic GMP and cyclic AMP on force of contraction in mammalian myocardium.