Naringin promotes positive inotropism in atrial tissue through β-AR/PKA-dependent pathway

Naringin is a flavonoid glycoside found in citrus fruits and grapes with a wide range of therapeutic actions. We aimed to study the inotropic effect of naringin on rat-isolated atria, dissecting intracellular mechanisms involved in this response. Concentration-response curves of naringin (0.003-6 mM) were obtained before and after pre-incubation with selective antagonists. Our results showed that naringin presented a biphasic inotropic response, with a positive inotropic effect at low and middle concentrations (0.003-2.0 mM), and a negative inotropic effect at high concentrations (above 3 mM). Pre-incubation with propranolol or atenolol (β-adrenergic receptors antagonists, β-AR), H89 (protein kinase-A inhibitor, PKA), nifedipine (L-type Ca2+ channel blocker), or ryanodine (ryanodine receptor inhibitor) fully abolished the positive inotropic effect induced by naringin. Pre-treatment of animals with reserpine, catecholamine-depleting drug, also prevented the increase of atrial contractility evoked by naringin. Altogether, we show that naringin causes a positive inotropic effect in isolated atria through β-AR/PKA-dependent pathway.