The Frank-Starling mechanism (heterometric autoregulation) plays a major role in intrinsic regulation of cardiac function. It has been demonstrated that, as in mammals (Prendergast et al., 1997) and in fish (Imbrogno et al., 2001) hearts, also in frog cardiac preparations Nitric Oxide (NO) affects the Frank-Starling response by making the heart more sensitive to preload increases (Tota et al., 2009).

Recently, Mazza and co-workers (2008) showed that the Chromogranin A (CGA)-derived peptide, Catestatin (bovine CGA_344-364), exerts a direct cardio-suppressive action in the isolated and perfused frog heart. This effect appeared mediated by a NO-cGMP pathway and required the functional integrity of Endocardial Endothelium (EE).

The aim of this work was to test if Catestatin influences the Frank-Starling response of the invitro working frog hearts and the eventual mechanism of action involved. Stroke Volume (SV) and Stroke Work (SW) were used as indexes of contractile activity.

We demonstrated that Catestatin significantly increases the sensitivity to filling pressure changes. This positive heterometric modulation was abolished by NO synthase, guanylate cyclase and protein kinase G (PKG) inhibitors and by EE functional damage, pointing to a mechanism of action mediated by an EE-NO-cGMP-PKG pathway.

These data suggest a novel paracrine/autocrine role of Catestatin as modulator of the Frank-Starling response in the frog heart.