Involvement of functional antagonism in the effects of adenosine antagonists and L-NAME in the rat isolated heart.
1. Adenosine and its analogues induced an increase in flow rate when infused into the rat isolated perfused heart. The agonist potency order obtained was 2-(rho-(2-carboxyethyl)phenethyl-amino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) > or = 5'-N-ethylcarboxamidoadenosine (NECA) > N6-cyclopentyladenosine = adenosine, although the maximal response obtained for CGS 21680 was only 70% of that achieved by NECA. NG-Nitro-L-arginine methyl ester (L-NAME), the nonselective adenosine antagonist 8-rho-(sulfophenyl)theophylline (8-SPT) and the A2a selective antagonist N-[2-(dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- diprophyl-1H-purin-8-yl)benzene sulfonamide (PD 115, 119) reduced responses to the adenosine agonists, but some of this reduction was shown to be due to a nonspecific decrease in flow rate as well as a specific inhibitory action. 2. When this functional antagonism is taken into account, the results suggest that the increase in flow rate induced by the adenosine agonists was mediated by A2 receptors, with the increase in flow rate induced by CGS 21680 mediated by A2a receptors, whereas that induced by NECA was mediated by A2b receptors. 3. L-NAME did not appear to have any effect on the increase in flow rate induced by the adenosine agonists, suggesting that these responses were probably endothelium independent and do not involve the nitric oxide pathway.
Lewis
C D
CD
School of Biological Sciences, University of Surrey, Guildford, United Kingdom.
Hourani
S M
SM
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000241:Adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000316:Adrenergic alpha-Agonists; D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009599:Nitroprusside; D010627:Phenethylamines; D010656:Phenylephrine; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D013449:Sulfonamides; D013806:Theophylline; D014665:Vasodilator Agents; C052023:N-(2-(dimethylamino)ethyl)-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C031433:8-(4-sulfophenyl)theophylline