Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart.

Background: Glucagon is thought to increase heart rate and contractility by stimulating glucagon receptors and increasing 3',5'-cyclic adenosine monophosphate (cAMP) production in the myocardium. This has been confirmed in animal studies but not in the human heart. The cardiostimulatory effects of glucagon have been correlated with the degree of cardiac dysfunction, as well as with the enzymatic activity of phosphodiesterase (PDE), which hydrolyses cAMP.

Does glucagon have a positive inotropic effect in the human heart?

Glucagon is considered to exert cardiostimulant effects, most notably the enhancement of heart rate and contractility, due to the stimulation of glucagon receptors associated with Gs protein stimulation which causes adenylyl cyclase activation and the consequent increase in 3',5'-cyclic adenosine monophosphate production in the myocardium. These effects have been extensively demonstrated in experimental studies in different animal species. However, efforts to extrapolate the experimental data to patients with low cardiac output states, such as acute heart failure or cardiogenic shock, have been disappointing.

Resveratrol enhances the inotropic effect but inhibits the proarrhythmic effect of sympathomimetic agents in rat myocardium.

Background: Resveratrol is a cardioprotective agent with known antiarrhythmic effects that has recently been shown to inhibit phosphodiesterase (PDE) enzyme activity. Thus, it is possible that resveratrol increases the inotropic effect of sympathomimetic agents, as PDE inhibitors do but, unlike other PDE inhibitors, its effect may not be accompanied by proarrhythmia due to its antiarrhythmic action. This work is aimed to test this hypothesis.

Single inhibition of either PDE3 or PDE4 unmasks β2-adrenoceptor-mediated inotropic and lusitropic effects in the left but not right ventricular myocardium of rat.

Cyclic nucleotide phosphodiesterase (PDE)3 and PDE4 provide the major PDE activity in cardiac myocytes and shape β1-adrenoceptor-dependent cardiac cAMP signaling but their role in regulating β2-adrenoceptor-mediated responses is less well known. We investigated potential differences in PDE3 and PDE4 activities between right (RV) and left (LV) ventricular myocardium, and their role in regulating β2-adrenoceptor effects. PDE3 activity in the microsomal fraction was lower in RV than in LV but was the same in the cytosolic fraction.