Hemodynamic Responses Elicited by Systemic Injections of Flavin Adenine Dinucleotide in Anesthetized Rats
| Autor: | Kevin Sandock, Tom P. Robertson, James N. Bates, Jonathan E. Graves, Maleka P. Hashmi-Hill, Stephen J. Lewis |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Flavin Mononucleotide Flavin mononucleotide Blood Pressure Vasodilation Pharmacology Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Heart Rate Muscarinic acetylcholine receptor Bradycardia medicine Animals heterocyclic compounds Cardiac Output Mesenteric arteries Flavin adenine dinucleotide Dose-Response Relationship Drug biology Receptors Purinergic P2 Antagonist Receptors Muscarinic Hindlimb Mesenteric Arteries Rats Nitric oxide synthase medicine.anatomical_structure chemistry Biochemistry Prostaglandin-Endoperoxide Synthases Flavin-Adenine Dinucleotide biology.protein Vascular Resistance Nitric Oxide Synthase Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Cardiovascular Pharmacology. 50:94-102 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/fjc.0b013e31805c162a |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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