Responses of rat and guinea pig hearts to glucagon. Lack of evidence for a dissociation between changes in myocardial cyclic 3'5'-adenosine monophosphate and contractility.

Previous studies have suggested that the lnotropic effects of glucagon on the guinea pig heart, but not on the rat heart, could be dissociated from its effects on cyclic AMP formation. We compared the effects of glucagon on working rat and guinea pig hearts to reinvestigate this proposed dissociation. When administered to spontaneously beating preparations, glucagon produced •imilar increases hi rate, but different increases in contractility, of rat and guinea pig hearts. ITie inotropic effects of glucagon on the rat heart -were greater in magnitude than those on the guinea pig heart. Glucagon (10"* to 3 x 10"' M) increased left ventricular pressure (LVP) and the rate of pressure development (dP/dt), and reduced the time-to-peak pressure (TPP) of both rat and guinea pig spontaneously beating hearts. Studies in which the chronotropic responses to glucagon (10"' M) were duplicated electronically showed that the inotropic effects on the spontaneously beating guinea pig heart were entirely frequency-dependent, whereas those on the rat heart were not. In addition, glucagon (10" M) markedly increased LVP, dP/dt, and ventricular cyclic AMP levels of the paced rat heart, but had no effect on any of these variables in the paced guinea pig heart. The results do not support the proposed dissociation between cyclic AMP generation and positive inotropic responses of the guinea pig heart to glucagon. They suggest further that the guinea pig heart exhibits regional differences in sensitivity to glucagon. Ore Rea 49: 21&-23S, 1981