Nitrite modulates contractility of teleost (Anguilla anguilla and Chionodraco hamatus, i.e. the Antarctic hemoglobinless icefish) and frog (Rana esculenta) hearts

Being the largest form of intravascular and tissue storage of nitric oxide (NO) and a signalling molecule itself,the nitrite anion (NO2−) has emerged as a key player in many biological processes. Since the heart is under animportant NO-mediated autocrine–paracrine control, in mammals the cardiac effects of nitrite are underintensive investigation. In contrast, nothing is known in non-mammalian vertebrates. We evaluated nitriteinfluence on cardiac performance in the perfused beating heart of three different cold-blooded vertebrates,i.e. two teleost fishes, the temperate red-blooded Anguilla anguilla, the Antarctic stenotherm, hemoglobinlessChionodraco hamatus (icefish), and the frog Rana esculenta. We showed that, under basal conditions, in allanimals nitrite influences cardiac mechanical performance, inducing negative inotropism in eel and frog,while being a positive inotrope in C. hamatus. In all species, these responses parallel the inotropic effects ofauthentic NO. We also demonstrated that the nitrite-dependent inotropic effects are i) dependent from NOsynthase (NOS) activity in fish; ii) sensitive to NO scavenging in frog; iii) cGMP/PKG-dependent in both eeland frog. Results suggest that nitrite is an integral physiological source of NO and acts as a signalling moleculein lower vertebrate hearts, exerting relevant inotropic actions through different species-specific mechanisms.