Paracrine modulation of cardiac performance: the frog heart as an ideal model

We have used the avascular in vitro working heart of Rana esculenta to study the paracrine role of Endocardial Endothelium (EE) as a source of nitric oxide (NO) and as sensor of luminal blood flow-related stimuli. We found that the EE, which contains the endothelial nitric oxide synthase (eNOS), under basal conditions produces NO in amounts sufficient to exert a negative inotropism on the myocardium via a cGMP-dependent mechanism. The NO signal is abrogated by the functional damage of the EE, indicating that EE transduces mechanical stimulation into NO release. We demonstrated an EE-dependent autoregulation of cardiac performance via receptor-mediated inotropic mechanisms involving ACh and endothelin-1 pathways. Both pathways require an intact EE and the involvement of NO-cGMP signalling. Taken together these data indicate the importance of the EE-mediated intracavitary modulation of cardiac performance