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.