Effects of 8-bromo-cyclic GMP on contraction and on inotropic response of ferret cardiac muscle

Abstract

The effects of guanosine 3':5'-cyclic monophosphate (cGMP) on cardiac contraction are not established. Using isolated electrically-stimulated ferret papillary muscle at 29 degrees C, 2.0 mM calcium we investigated the effects of 8-Bromo-cGMP on (a) basal contraction for comparison with the effects of reduction in extracellular calcium or of reduction in resting muscle length; (b) contraction of preparations stimulated by isoprenaline, the dihydropyridine calcium agonist Bay K8644 or post-extrasystolic potentiation. 8-Bromo-cGMP (0.1 mM) induced a small significant reduction in isometric twitch tension (TT) (7%), isotonic shortening (PS) (6%) and in twitch duration, but had no effect on maximum unloaded shortening velocity (Vmax) or rate of tension development (+dT/dt). Reduction in muscle length induced a similar immediate effect on contraction. Reduction of extracellular calcium (2.0 mM to 1.25 mM) reduced TT by 24% and PS by 14% as well as Vmax (19%) and +dT/dt (29%), but did not alter twitch duration. Bay K8644 (0.01 to 10 microM) produced increases in TT, +dT/dt, PS and twitch duration each of which was significantly reduced in the presence of 8-Bromo-cGMP (0.1 mM). 8-Bromo-cGMP had no effect on the responses to isoprenaline 1 nM to 100 microM--which increased TT, +dT/dt and PS but markedly reduced twitch duration--nor on post-extrasystolic potentiation which increased TT and +dT/dt but slightly reduced twitch duration. These results show that 8-Bromo-cGMP induces changes similar to the immediate effects of reduction in resting muscle length, and reduces the positive inotropic effects of Bay K8644 but not those of isoprenaline or post-extrasystolic potentiation.