Late phase of nitroglycerin-induced coronary vasodilatation blunted by inhibition of prostaglandin synthesis.
In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of increasing doses of indomethacin or naproxen on the coronary and systemic hemodynamic responses to a 5 microgram intracoronary injection of nitroglycerin (NTG) were evaluated. The integrated areas of NTG-induced coronary vasodilatation were reduced after administration of indomethacin or naproxen. The extent of this reduction was increased progressively by augmenting the dose of indomethacin and naproxen up to 1.5 and 7 mg/kg, respectively. We also assessed the extent of cyclooxygenase inhibition induced by indomethacin or naproxen through the radioimmunoassay of thromboxane B2, which reflects thrombin-induced activation of platelet thromboxane A2 production during whole blood clotting. The level of inhibition progressively increased and complete inhibition was attained with 1.5 mg/kg indomethacin and 7 mg/kg naproxen. Further increase in dosage failed to induce further reduction of integrated areas of coronary vasodilatation, and a correlation was found between the extent of the reduction of the integrated areas of coronary vasodilatation and the dose of indomethacin (r = .828, n = 35, p less than .001) or naproxen (r = .729, n = 35, p less than .001). Finally, the NTG-induced maximum fall in coronary perfusion pressure remained unmodified after inhibition of prostaglandin synthesis, but there was a faster return of the perfusion pressure to the basal value.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009288:Naproxen / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D014664:Vasodilation
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D009288:Naproxen; D005996:Nitroglycerin; D007213:Indomethacin