The evolutionary functions of cardiac NOS/NO in vertebrates tracked by fish and amphibian paradigms

During early ectotherm vertebrate evolution the heart was redesigned as a high pressure pump adaptedto perfuse larger body sizes. To compensate the consequent higher organ complexity and heterogeneity(ventricular myoarchitecture and blood supply), conceivably the three principal cardiac cell components,the endocardium, the contractile myocardium and the epicardium recruited and diversified the cardiacNOS system for functioning not only as a major modulator, but also as a spatio-temporal integrator ofheart function. In the context of NOS isoform evolution, we will use fish and amphibian paradigms toillustrate major aspects of cardiac spatial and temporal integration achieved by the NOS/NO systems. Thismay reveal a primordial cardiac NOS/NO function, allocating it in a wider biological framework than sofar envisioned.