Background and Aims– 

The two appetite inhibiting proglucagon-derived peptides, namely GLP-1 and GLP-2, are involved in the integrated cardiovascular-gastrointestinal response. Both are produced in enteroendocrine cellsand secreted in a nutrient-dependent manner (Dubé et al., 2007). Although a cardiovascular action has been proposed for GLP-1 (Yamamoto et al., 2002), the direct cardiac influence of GLP-2 is still unexplored. This study aims to analyze the effects and the mechanism of action of GLP-2 on both the basal cardiac performance and the coronary reactivity of the rat heart, considered as a prototypic mammalian heart.

Methods and results– 

By immunoblotting and QT-PCR we revealed, for the first time, the presence of GLP-2 cardiac receptors. Application of Langendorff perfusion technique showed that GLP-2 induces a biphasic effect: positive inotropism and lusitropism at lower concentrations and negative inotropism and lusitropism at higher concentrations. The peptide also constricts the coronaries in a dose-dependent manner. Treatment with papaverine, used as a coronary dilator, did not influence GLP-2 cardiotropic effects, suggesting that negative inotropism and lusitropism were independent from coronary reactivity. We also found that GLP-2 effects are independent by GPL-1 receptors since persisted after receptor inhibition.

Conclusions– 

Our results suggest for the first time that GLP-2, by acting on cardiac receptors, directly modulates the performance of the rat heart, by acting on both the myocardium and the coronaries. These observations are of relevance since they further support the possibility that a neurohumoral gastrointestinal-cardiac axis contributes to modulate heart function in relation to the nutritional state.