Ischaemic cardiac hyperaemia: role of nitric oxide and other mediators.
In the perfused guinea-pig heart reactive hyperaemia (RH) after occlusion of coronary flow (1-60 s) was inhibited by 100-60% with NG-nitro-L-arginine (100 microM) and to a lesser extent (by 35%) after 8-phenyltheophylline (10 microM), but not by indomethacin (5 microM). Inhibition of adenosine deaminase by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (5 microM) not only increased the concentration of adenosine in the coronary perfusate, but also prolonged the duration of RH. RH induced cardiac generation of prostacyclin, nitric oxide and adenosine as indicated by the appearance of 6-keto-PGF1 alpha, cyclic GMP, adenosine, inosine, hypoxanthine, xanthine and urate in the perfusate. Only NO and adenosine, but not prostacyclin, were responsible for RH. RH after short-term (1-10 s) coronary occlusion was mediated by NO, whereas adenosine and NO maintained RH that followed after longer (20 s-10 min) periods of cardiac ischaemia. Prostacyclin never participated in the mediation of RH.
Gryglewski
R J
RJ
Chair of Pharmacology, Jagiellonian University, Cracow, Poland.
Chlopicki
S
S
Niezabitowski
P
P
Jakubowski
A
A
Lomnicka
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004562:Electrocardiography; D016232:Endothelins / Q000037:antagonists & inhibitors; D011464:Epoprostenol / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D006940:Hyperemia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D016232:Endothelins; D011448:Prostaglandin Antagonists; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D013806:Theophylline; D011464:Epoprostenol; C028322:8-phenyltheophylline; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000241:Adenosine; D007213:Indomethacin