Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats

Maleka P Hashmi-Hill; Kevin Sandock; James N Bates; Tom P Robertson; Stephen J Lewis

doi:10.1097/FJC.0b013e31805c1646

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Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats

Journal article

Peer reviewed

Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats

Maleka P Hashmi-Hill, Kevin Sandock, James N Bates, Tom P Robertson and Stephen J Lewis

Journal of cardiovascular pharmacology, Vol.50(2), pp.142-154

08/2007

DOI: 10.1097/FJC.0b013e31805c1646

PMID: 17703130

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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.

NG-Nitroarginine Methyl Ester - pharmacology

Cysteine - analogs & derivatives

Nitric Oxide - biosynthesis

Injections, Intravenous

Flavin-Adenine Dinucleotide - administration & dosage

Acetylcholine - pharmacology

Flavin-Adenine Dinucleotide - pharmacology

Receptor, Muscarinic M3 - drug effects

Nitric Oxide Synthase - drug effects

Receptor, Muscarinic M3 - metabolism

Aorta, Thoracic - metabolism

Rats

Cysteine - drug effects

Male

Nitroprusside - pharmacology

S-Nitrosothiols - metabolism

Rats, Sprague-Dawley

Animals

Endothelium, Vascular - metabolism

Cysteine - metabolism

Nitric Oxide Synthase - metabolism

Radioligand Assay

Vasodilation - drug effects

Details

Title: Subtitle: Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats
Creators: Maleka P Hashmi-Hill - Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia 30602-7389, USA
Kevin Sandock
James N Bates
Tom P Robertson
Stephen J Lewis
Resource Type: Journal article
Publication Details: Journal of cardiovascular pharmacology, Vol.50(2), pp.142-154
Publisher: United States
DOI: 10.1097/FJC.0b013e31805c1646
PMID: 17703130
ISSN: 0160-2446
eISSN: 1533-4023
Language: English
Date published: 08/2007
Academic Unit: Anesthesia
Record Identifier: 9984006359602771

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