Smith E F, Schmunk G A, Lefer A M
J Cardiovasc Pharmacol. 1981 Jul-Aug;3(4):791-800. doi: 10.1097/00005344-198107000-00012.
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.
在离体灌注的猫冠状动脉中，研究了六种非甾体抗炎药——甲氯芬那酸、吲哚美辛、氟比洛芬、萘普生、布洛芬和乙酰水杨酸——抑制血栓素激动剂环戊烷血栓素A2（CTA2）诱导的冠状动脉收缩的能力。在恒定流量下，7.5 nM CTA2使冠状动脉灌注压升高33±3 mmHg（n = 20）。甲氯芬那酸钠在0.34 μM时使7.5 nM CTA2诱导的血管收缩降低2%（无统计学意义），在3.4 μM时降低38%（无统计学意义），在34 μM时降低99%（p<0.025）。甲氯芬那酸的IC50为5.4 μM；吲哚美辛、氟比洛芬、萘普生、布洛芬和乙酰水杨酸的IC50分别为42、150、250、485和610 μM。将细胞外钙浓度提高到10 mM可完全逆转对CTA2诱导的冠状动脉收缩的抑制作用。此外，数据表明，抗炎药对CTA2诱导的冠状动脉收缩的抑制作用可能是由血栓素受体拮抗或钙通道阻滞来解释的。
