Hemodynamic responses elicited by systemic injections of flavin adenine dinucleotide in anesthetized rats.
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.
Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602-7389, USA.
Maleka P
MP
Hashmi-Hill
Jonathan E
JE
Graves
Kevin
K
Sandock
James N
JN
Bates
Tom P
TP
Robertson
Stephen J
SJ
Lewis
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced*; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005486:Flavin Mononucleotide / Q000008:administration & dosage / Q000494:pharmacology*; D005182:Flavin-Adenine Dinucleotide / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb; D008297:Male; D008638:Mesenteric Arteries; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects*
D011976:Receptors, Muscarinic; D018048:Receptors, Purinergic P2; D005182:Flavin-Adenine Dinucleotide; D005486:Flavin Mononucleotide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases