Inhibition by nitroglycerin of canine platelet aggregation and cyclic flow reductions in stenosed coronary arteries.
The aim of this study was to investigate the hypothesis that the action of nitroglycerin on acute coronary arterial diseases is due to the inhibition of platelet aggregation. Anesthetized open chest beagle dogs under artificial respiration were used. Cyclic flow reductions were induced by partial occlusion of the left anterior descending coronary artery at the site of endothelial injury. Nitroglycerin (20 mu g/kg followed by 3 mu g/kg/min, i.v.) attenuated the frequency and severity of cyclic flow reductions but did not recover the reduced coronary blood flow to baseline. Nitroglycerin completely abolished cyclic flow reductions in 3 of 7 animals. In other animals, intravenous injection of the same dose of nitroglycerin inhibited ex vivo platelet aggregation evoked by adenosine diphosphate (ADP, 10 mu M). However, nitroglycerin failed to suppress the platelet aggregation induced by a combination of ADP (1 mu M) with 5-hydroxytryptamine (5-HT, 1 mu M). In other experiments, diltiazem (calcium antagonist; 0.1 mg/kg, i.v.) did not affect cyclic flow reductions, and DP-1904 (inhibitor of thromboxane A2 synthetase; 1 mg/kg, i.v.) completely abolished cyclic flow reductions in 6 of 7 animals. These results indicate that nitroglycerin can inhibit cyclic flow reductions in part by attenuating the action of ADP on platelet aggregation, and that nitroglycerin is less potent than thromboxane A2 synthetase inhibitor in this model.
Tanaka
T
T
Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Morishima
Y
Y
Watanabe
K
K
Takahashi
M
M
Shibano
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D013764:Tetrahydronaphthalenes; D014665:Vasodilator Agents; C056295:nafagrel; D013930:Thromboxane-A Synthase; D004110:Diltiazem; D005996:Nitroglycerin