PMID: 12079003Jun 25, 2002Paper

Effects of adenosine receptor agonists on guinea-pig isolated working hearts and the role of endothelium and NO

The Journal of Pharmacy and Pharmacology
Helen L MaddockNassirah Khandoudi

Abstract

The hypothesis that the coronary vasodilator effects of adenosine receptor agonists are independent of the vascular endothelium or mediators derived therefrom was examined in guinea-pig isolated working hearts. Adenosine receptor agonists, 5'-(N-ethylcarboxamido)-adenosine (NECA; two-fold selective for A2 over A1 receptors), 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680; A2A selective), N6-cyclopentyl-adenosine (CPA; A1 selective) and N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA; A3 selective), were infused (3 x 10(-7) M) after endothelium removal by passing oxygen through the coronary circulation. In spontaneously beating hearts, CGS21680 and NECA increased, while CPA decreased, coronary flow. NECA and CPA reduced heart rate, left ventricular pressure and aortic output. The nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NOARG; 3 x 10(-5) M) abolished the vasodilatation by NECA but not CGS21680, indicating that nitric oxide (NO) of a non-endothelial source mediated the NECA response. Coronary vasodilatation by CGS21680 was inhibited bythe A2A receptor antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo [2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385). Indome...Continue Reading

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Citations

Oct 3, 2003·European Journal of Pharmacology·Helen L MaddockKenneth J Broadley
Apr 4, 2012·Journal of Medicinal Chemistry·Pier Giovanni BaraldiKatia Varani
Feb 17, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Jiang-Ning YangBertil B Fredholm
Jun 15, 2013·Pharmacology & Therapeutics·John P HeadrickJason N Peart
Oct 19, 2011·Journal of Molecular and Cellular Cardiology·Andreas DeussenWilliam Chilian
Nov 26, 2010·Biochimica Et Biophysica Acta·John P HeadrickLuke J Haseler
May 10, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Joana Beatriz Sousa, Carmen Diniz
Mar 7, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Huda E TawfikS Jamal Mustafa
Aug 16, 2017·European Journal of Pharmacology·Hardip SandhuHelen Maddock

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