title: Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats.
abstract: This study determined whether flavin adenine dinucleotide (FAD) may elicit vasodilation in conscious rats via release of preformed endothelium-derived nitrosyl factors. Injections 1-6 (inj(1-6)) of FAD (2.5 micromol/kg, IV) elicited pronounced and equivalent vasodilator responses in saline-treated rats. Inj(1) of FAD elicited pronounced vasodilation in L-NAME-treated rats pretreated with the nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine (L-NAME; 50 micromol/kg, IV), whereas Inj(2-6) elicited progressively smaller responses such that inj(6) elicited minor responses. The vasodilator responses elicited by the endothelium-dependent agonist, acetylcholine, were markedly attenuated in L-NAME-treated rats that had received inj(1-6) of FAD but not in saline-treated rats that had received inj(1-6) of FAD. The vasodilator actions of L-S-nitrosocysteine and the NO donor, sodium nitroprusside, were not diminished after the injections of FAD in saline- or in L-NAME-treated rats. Binding studies demonstrated that the densities of muscarinic M3 receptors were increased in thoracic aorta endothelium of rats treated with L-NAME + inj(1-6) of saline or L-NAME + inj(1-6) of FAD as compared to rats treated with saline + inj(1-6) of saline or saline + inj(1-6) of FAD. The progressive loss of response to injections of FAD in L-NAME-treated rats coupled with the loss of response to acetylcholine suggests that FAD elicits the use-dependent depletion of vesicular pools of nitrosyl factors in endothelial cells that cannot be replenished in the absence of NO synthesis.
authors: Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia 30602-7389, USA.
authors: Maleka P
authors: MP
authors: Hashmi-Hill
authors: Kevin
authors: K
authors: Sandock
authors: James N
authors: JN
authors: Bates
authors: Tom P
authors: TP
authors: Robertson
authors: Stephen J
authors: SJ
authors: Lewis
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000187:drug effects* / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D043587:Receptor, Muscarinic M3; D026403:S-Nitrosothiols; D005182:Flavin-Adenine Dinucleotide; D009599:Nitroprusside; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D019001:Nitric Oxide Synthase; D003545:Cysteine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester