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°C, 2.0 m m 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 m m) 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 ( V max) or rate of tension development ( + dτ dt ). Reduction in muscle length induced a similar immediate effect on contraction. Reduction of extracellular calcium (2.0 m m to 1.25 m m) reduced TT by 24% and PS by 14% as well as V max (19%) and + dτ dt (29%), but did not alter twitch duration. Bay K8644 (0.01 to 10 μ m) produced increases in TT, + dτ dt , PS and twitch duration each of which was significantly reduced in the presence of 8-Bromo-cGMP (0.1 m m). 8-Bromo-cGMP had no effect on the responses to isoprenaline 1 n m to 100 μ m—which increased TT, + dτ dt and PS but markedly reduced twitch duration—nor on post-extrasystolic potentiation which increased TT and + dτ 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.