The cardioprotective effects of the thromboxane receptor antagonist SQ 30,741 are not reversed by aspirin.
A previous study indicated that 5 mg/kg aspirin can reverse the cardioprotective effects of thromboxane A2 synthetase inhibitors. We determined in the present study if this dose of aspirin can also reverse the protective effects of the thromboxane A2/PGH2 receptor antagonist SQ 30,741 in the same model of coronary occlusion and reperfusion. Anesthetized dogs were subjected to 90 min of coronary occlusion and 5 h of reperfusion and were treated with vehicle or SQ 30,741 (1 mg/kg + 1 mg/kg/h) 10 min after the onset of coronary occlusion. SQ 30,741 was given to dogs pretreated with aspirin (5 mg/kg, 24 h presurgery) or vehicle. SQ 30,741 significantly reduced infarct size compared to vehicle treatment (58% vs 35% of the left ventricular area at risk for vehicle and SQ 30,741 groups respectively) and aspirin did not reverse this. These anti-ischemic effects occurred despite a lack of change in collateral flow. Thus, important differences in mechanism of action between thromboxane synthesis inhibitors and receptor antagonists seem to exist and further work in this area is warranted.
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey.
Parham
C S
CS
Schumacher
W A
WA
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001784:Blood Gas Analysis; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D012039:Regional Blood Flow / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2; D001241:Aspirin