NOS3 and atrial fibrillation: The AF patients present downregulation of endothelial nitric oxide synthase (eNOS) (59), accounting for reduced nitric oxide-dependent vasodilation, as well as a potential influence on neurohumoral factors (60) [elevated levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which mediate a shift of the vascular tone toward vasoconstriction], and increased sympathetic tone (61) (which increases coronary vascular resistance, reducing coronary flow reserve in response to increased myocardial energy demand).