Inhibitory effect of quinacrine on myocardial reactive hyperemia in the dog.
We investigated the effect of quinacrine, a phospholipase A2 inhibitor, on myocardial reactive hyperemic response after 5-, 10- and 20-sec coronary occlusions and adenosine-induced coronary vasodilatation in perfused dog hearts in situ. Continuous infusions of quinacrine (30-300 micrograms/min) into the left coronary artery significantly reduced both reactive hyperemic response and increase in coronary blood flow produced by intracoronary injections of adenosine (1-30 micrograms) without significant effect on basal coronary blood flow, perfusion pressure and heart rate. Neither acetylcholine- nor verapamil-induced increases in coronary blood flow were modified by quinacrine. The reactive hyperemic response and the vasodilatory effect of adenosine were both reduced by intracoronary infusions of theophylline (100-1000 micrograms/min). The inhibitory effect of theophylline on the reactive hyperemic response was less prominent than that of quinacrine, whereas the vasodilatory effect of adenosine was reduced to the same extent by both drugs. Intracoronary infusions of indomethacin (a cyclooxygenase inhibitor), phenidone (an inhibitor of both cyclooxygenase and lipoxygenase) and nordihydroguaiaretic acid (a lipoxygenase inhibitor) did not affect the reactive hyperemic response. The present results support the hypothesis that adenosine may be a mediator of myocardial reactive hyperemia and suggest that other factors, possibly phospholipase products, may also contribute to this phenomenon. We were unable to define the mechanism involved; however, it can be excluded that cyclooxygenase and lipoxygenase products of arachidonic acid contribute to myocardial reactive hyperemia.
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D002396:Catechols / Q000494:pharmacology; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006940:Hyperemia / Q000188:drug therapy*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol; D011720:Pyrazoles / Q000494:pharmacology; D011796:Quinacrine / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002396:Catechols; D011720:Pyrazoles; D009637:Masoprocol; D013806:Theophylline; D014700:Verapamil; D011796:Quinacrine; C015429:phenidone; D000241:Adenosine; D000109:Acetylcholine; D007213:Indomethacin