a Sección de Estudios de Posgrado e Investigación , Escuela Superior de Medicina, Instituto Politécnico Nacional , México , D.F. , México.
b Departamento de Biología Celular , Instituto Nacional de Perinatología , México , D.F. , México.
Clin Exp Hypertens. 2017;39(3):210-219. doi: 10.1080/10641963.2016.1226895.
In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas. Enzyme immunoassay data supported direct evidence of phenylephrine-stimulated release of prostanoids (PGI, PGE, and PGF) by thoracic and abdominal aortas without endothelium, and their almost complete inhibition by 1 μM indomethacin. Isometric force measurements established that 10 μM indomethacin-but no lower concentrations-inhibited the contractions evoked by phenylephrine in endothelium-denuded abdominal aorta. In this preparation, 10 μM indomethacin also depressed the contractions provoked by angiotensin II and high K (80 mM). In fact, indomethacin (up to 1 mM) caused concentration-dependent reductions in all abovementioned contractile responses. In endothelium-denuded thoracic aortas, however, only 1 mM indomethacin significantly depressed the contractile activity stimulated by either phenylephrine, angiotensin II, or high K. Hence, there was a clear quantitative difference in response to indomethacin between abdominal and thoracic aortas without endothelium. Altogether, the results indicate that prostanoids induced by phenylephrine in abdominal and thoracic aortas were derived from non-endothelial COX-mediated metabolism; notably, the decrease in prostanoid synthesis could not account for the inhibition of vasoconstrictor responses by indomethacin: Through COX-independent actions, indomethacin inhibited aortic smooth muscle contractility.
在去内皮的大鼠腹主动脉（而非胸主动脉）中，非选择性环氧化酶（COX）抑制剂吲哚美辛抑制了α-肾上腺素能激动剂引起的收缩反应，这些反应假设是由前列腺素介导的。我们旨在确定这些由α-肾上腺素受体激活释放的非内皮源性收缩性前列腺素。我们使用去内皮的大鼠腹主动脉和胸主动脉进行生化和功能分析。Western blot 分析表明，COX-1 和 COX-2 蛋白水平在去内皮的大鼠腹主动脉和胸主动脉中分别相当。酶免疫测定数据支持直接证据表明，去内皮的胸主动脉和腹主动脉在没有内皮的情况下，苯肾上腺素刺激前列腺素（PGI、PGE 和 PGF）的释放，而 1 μM 吲哚美辛几乎完全抑制了这种释放。等长力测量表明，10 μM 吲哚美辛（而非更低浓度）抑制了去内皮的大鼠腹主动脉中苯肾上腺素引起的收缩反应。在这种制剂中，10 μM 吲哚美辛还抑制了血管紧张素 II 和高 K（80 mM）引起的收缩反应。事实上，吲哚美辛（高达 1 mM）引起了所有上述收缩反应的浓度依赖性降低。然而，在去内皮的大鼠胸主动脉中，只有 1 mM 吲哚美辛显著抑制了苯肾上腺素、血管紧张素 II 或高 K 刺激引起的收缩活性。因此，去内皮的大鼠腹主动脉和胸主动脉对吲哚美辛的反应存在明显的定量差异。总之，这些结果表明，苯肾上腺素在大鼠腹主动脉和胸主动脉中诱导的前列腺素来自非内皮 COX 介导的代谢；值得注意的是，前列腺素合成的减少不能解释吲哚美辛对血管收缩反应的抑制作用：通过 COX 非依赖性作用，吲哚美辛抑制了主动脉平滑肌的收缩性。
