flavin-adenine-dinucleotide and Bradycardia

Flavin adenine dinucleotide (FAD) elicits an endothelium-dependent vasodilation in isolated rat mesenteric beds via activation of P2Y-purinoceptors. The aims of this study were to characterize the hemodynamic responses elicited by systemic injections of FAD and flavin mononucleotide (FMN) in anesthetized rats and to determine the role of nitric oxide synthase (NOS), cyclooxygenase, P2Y/P2X-purinoceptors, and muscarinic receptor in these responses. FAD (0.05-1.0 micromol/kg, iv) elicited dose-dependent decreases in heart rate (HR), mean arterial blood pressure (MAP), and hindquarter vascular resistance (HQR), whereas it elicited an initial increase and then a decrease in mesenteric (MR) vascular resistance. The FAD-induced responses were not affected by the P2Y/P2X-purinoceptor antagonist suramin, the muscarinic receptor antagonist methyl-atropine, or the cyclooxygenase inhibitor indomethacin. The vasodilator actions of FAD were unaffected by the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), whereas the bradycardia elicited by higher doses of FAD were diminished by L-NAME. FMN did not elicit hemodynamic responses in the absence or presence of L-NAME. In summary, FAD-induced bradycardia depends, in part, on the activation of NOS, whereas the vasodilator actions of FAD are not obviously due to newly synthesized nitrosyl factors. These findings and those in our companion manuscript support the concepts that the adenine moiety confers biological activity to FAD, which releases preformed pools of nitrosyl factors.

Topics: Animals; Blood Pressure; Bradycardia; Cardiac Output; Dose-Response Relationship, Drug; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Heart Rate; Hindlimb; Male; Mesenteric Arteries; Nitric Oxide Synthase; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Receptors, Purinergic P2; Vascular Resistance; Vasodilation

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Bradycardia; Dextrans; Electrocardiography; Energy Metabolism; Flavin-Adenine Dinucleotide; Glycogen; Lysine; Microcirculation; Mitochondria, Muscle; Molecular Weight; Myocardium; NAD; Oxidative Phosphorylation; Oxygen Consumption; Phosphorus; Phosphorylases; Rabbits; Stimulation, Chemical; Succinates; Vasopressins