Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats.
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.
Hashmi-Hill
Maleka P
MP
Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia 30602-7389, USA.
Sandock
Kevin
K
Bates
James N
JN
Robertson
Tom P
TP
Lewis
Stephen J
SJ
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*
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