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.

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Abstract
The inotropic effects of glucagon on the guinea pig heart, but not on the rat heart, could be dissociated from its effects on cAMP formation. The effects were compared of glucagon on working rat and guinea pig hearts to reinvestigate this proposed dissociation. When administered to spontaneously beating preparations, glucagon produced similar increases in rate, but different increases in contactility, of rat and guinea pig hearts. The inotropic effects of glucagon on the rat heart were greater in magnitude than those on the guinea pig heart. Glucagon (10-9 to 3 .times. 10-7 M) increased left ventricular pressure (LVP) and the rate of pressure development (dP/dt), and reduced the time-to-peak (TPP) of both rat and guinea pig spontaneously beating hearts. Studies in which the chronotropic responses to glucagon (10-7 M) were duplicated electronically showed that the inotropic effects on the spontaneously beating guinea pig heart were entirely frequency-dependent, but those on the rat heart were not. Glucagon (10-7 M) markedly increased LVP, dP/dt and ventricular cAMP 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 cAMP generation and positive inotropic responses of the guniea pig heart to glucagon. The guinea pig heart exhibits regional differences in sensitivity to glucagon.