Antagonism of thromboxane analog-induced vasoconstriction by non-steroidal anti-inflammatory agents.
The ability of six non-steroidal anti-inflammatory agents--meclofenamate, indomethacin, flurbiprofen, naproxen, ibuprofen, and acetylsalicylic acid--to inhibit coronary constriction induced by the thromboxane agonist carbocyclic thromboxane A2 (CTA2) was studied in isolated perfused cat coronary arteries. At constant flow, 7.5 nM CTA2 increased coronary artery perfusion pressure by 33 +/- 3 mm Hg (n = 20). Sodium meclofenamate reduced 7.5 nM CTA2-induced vasoconstriction by 2% at 0.34 microM (ns), 38% at 3.4 microM (ns), and 99% at 34 microM (p less than 0.025). The IC50 for meclofenamate was 5.4 microM; the IC50 for indomethacin, flurbiprofen, naproxen, ibuprofen, and acetylsalicylic acid was 42, 150, 250, 485, and 610 microM, respectively. Increasing the external calcium concentration to 10 mM completely reversed the inhibition of CTA2-induced coronary vasoconstriction. Furthermore, the data suggest that inhibition of CTA2-induced coronary vasoconstriction by anti-inflammatory agents may be explained either by thromboxane receptor antagonism or calcium channel blockade.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D013931:Thromboxanes; C024587:thromboxane A2, carbocyclic; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D009288:Naproxen; D005480:Flurbiprofen; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin