Intracoronary administration of adenosine triphosphate increases coronary blood flow and attenuates the severity of myocardial ischemic injury in dogs.
ATP generates nitric oxide (NO) via activation of P2y receptors, and is degraded to adenosine. This study was undertaken to examine whether ATP causes coronary hyperemic flow via purinoceptors-, NO- and adenosine-dependent mechanisms, and attenuates the severity of contractile and metabolic dysfunction in the ischemic myocardium. In the non-ischemic canine hearts, the infusions of ATP into the coronary artery dose-dependently increased coronary blood flow. The levels of adenosine and end-product of NO in coronary venous blood over the arterial blood also increased. This hyperemic flow was partially attenuated by either 8-sulfophenyltheophylline (8SPT) or L(omega)-nitro arginine methyl ester (L-NAME), and completely blocked by the treatment with 8SPT, L-NAME and suramin (SRM). During myocardial ischemia, exogenous ATP increased coronary blood flow, and attenuated myocardial metabolic and contractile dysfunction, which was completely blunted by the treatment with 8SPT, L-NAME and SRM. We conclude that exogenous ATP increases coronary blood flow in the non-ischemic and ischemic myocardium mainly via either NO- or adenosine-dependent mechanisms.
Kitakaze
M
M
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan. kitakaze@medone.med.osaka-u.ac.jp
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Komamura
K
K
Minamino
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Kosaka
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Kuzuya
T
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Hori
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D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D011983:Receptors, Purinergic / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000097:blood
D004791:Enzyme Inhibitors; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D009569:Nitric Oxide; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine