Hemodynamic responses elicited by systemic injections of flavin adenine dinucleotide in anesthetized rats

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

doi:10.1097/FJC.0b013e31805c162a

Back

Hemodynamic responses elicited by systemic injections of flavin adenine dinucleotide in anesthetized rats

Journal article

Peer reviewed

Hemodynamic responses elicited by systemic injections of flavin adenine dinucleotide in anesthetized rats

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

Journal of cardiovascular pharmacology, Vol.50(1), pp.94-102

07/2007

DOI: 10.1097/FJC.0b013e31805c162a

PMID: 17666921

View Online

Abstract

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.

Hindlimb

Vascular Resistance

Flavin-Adenine Dinucleotide - administration & dosage

Flavin-Adenine Dinucleotide - pharmacology

Cardiac Output - drug effects

Nitric Oxide Synthase - drug effects

Rats

Male

Receptors, Muscarinic - metabolism

Rats, Sprague-Dawley

Dose-Response Relationship, Drug

Flavin Mononucleotide - pharmacology

Heart Rate - drug effects

Bradycardia - chemically induced

Animals

Flavin Mononucleotide - administration & dosage

Prostaglandin-Endoperoxide Synthases - metabolism

Receptors, Purinergic P2 - metabolism

Mesenteric Arteries

Blood Pressure - drug effects

Nitric Oxide Synthase - metabolism

Vasodilation - drug effects

Details

Title: Subtitle: Hemodynamic responses elicited by systemic injections of flavin adenine dinucleotide in anesthetized rats
Creators: Maleka P Hashmi-Hill - Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602-7389, USA
Jonathan E Graves
Kevin Sandock
James N Bates
Tom P Robertson
Stephen J Lewis
Resource Type: Journal article
Publication Details: Journal of cardiovascular pharmacology, Vol.50(1), pp.94-102
Publisher: United States
DOI: 10.1097/FJC.0b013e31805c162a
PMID: 17666921
ISSN: 0160-2446
eISSN: 1533-4023
Language: English
Date published: 07/2007
Academic Unit: Anesthesia
Record Identifier: 9984006486802771

Metrics

24 Record Views

4 Times Cited - Web of Science