Nitrite is a positive modulator of the Frank-Starling response in the vertebrate heart

Evidence from both mammalian and non-mammalian vertebrates indicates that intracardiac nitric oxide (NO) facilitates myocardial relaxation, ventricular diastolic distensibility and consequently the Frank-Starling response, i.e. the preload-induced increase of cardiac output. Since nitrite ion (NO(2)(-)), the major storage pool of bioactive NO, recently emerged as a cardioprotective endogenous modulator, we explored its influence on the Frank-Starling response in eel, frog and rat hearts, used as paradigms of fish, amphibians and mammals, respectively. We demonstrated that, like NO, exogenous nitrite improves the Frank-Starling response in all species as indicated by an increase of Stroke Volume and Stroke Work (eel and frog) and of Left Ventricular (LV) Pressure and LVdP/dtmax (rat), used as indexes of inotropism. Unlike in frog and rat, in eel the positive influence of nitrite appeared to be dependent by NOS inhibition. In all species, the effect resulted sensitive to NO scavengers, independent on nitroxyl anion, and mediated by a cGMP/PKG-dependent pathway. Moreover, the nitrite treatment increased S-nitrosylation of lower molecular weight proteins in cytosolic and membrane fractions. These results suggest that nitrite acts as a physiological source of NO modulating, through different species-specific mechanisms, the stretch-induced intrinsic regulation of the vertebrate heart