Baber Syed R, Champion Hunter C, Bivalacqua Trinity J, Hyman Albert L, Kadowitz Philip J
Department of Pharmacology, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, La 70112, USA.
Circulation. 2003 Aug 19;108(7):896-901. doi: 10.1161/01.CIR.0000084536.87322.BB. Epub 2003 Aug 4.
Prostanoid synthesis by the cyclooxygenase (COX)-2 pathway plays an important role in inflammation, and recent studies have shown the presence of COX-2 in the normal rat lung. However, the role of COX-2 in the generation of vasoactive prostanoids in the rat is uncertain. In the present study, the hypothesis that synthesis of vasoactive prostanoids via the COX-2 pathway can alter pulmonary and systemic vascular resistance was investigated, and the effects of selective COX-2 inhibitors on pulmonary and systemic responses to the prostanoid precursor arachidonic acid were examined in the anesthetized rat with a recently developed right-heart catheterization technique.
Injections of arachidonic acid caused dose-related increases in pulmonary vascular resistance and decreases in systemic vascular resistance. These responses were attenuated by selective COX-2 inhibitors and a selective COX-1 inhibitor, whereas responses to exogenous prostanoids were not altered. Nimesulide or NS-398 did not alter arachidonic acid-induced platelet aggregation in rat platelet-rich plasma. Western blot analysis and immunostaining showed the expression of both COX isoforms in the rat lung.
The results of these experiments suggest that arachidonic acid is converted into vasoactive prostanoids by the COX-2 and COX-1 pathway in the pulmonary and peripheral vascular beds in the rat and that TXA2 is a major prostanoid formed in the normal rat lung.
环氧化酶（COX）-2途径合成前列腺素在炎症中起重要作用，最近的研究表明正常大鼠肺中存在COX-2。然而，COX-2在大鼠血管活性前列腺素生成中的作用尚不确定。在本研究中，研究了通过COX-2途径合成血管活性前列腺素可改变肺血管和体循环血管阻力的假说，并采用最近开发的右心导管插入术，在麻醉大鼠中检测了选择性COX-2抑制剂对肺和全身对前列腺素前体花生四烯酸反应的影响。
注射花生四烯酸导致肺血管阻力呈剂量依赖性增加，体循环血管阻力降低。这些反应被选择性COX-2抑制剂和选择性COX-1抑制剂减弱，而对外源性前列腺素的反应未改变。尼美舒利或NS-398不改变花生四烯酸诱导的大鼠富血小板血浆中的血小板聚集。蛋白质印迹分析和免疫染色显示大鼠肺中两种COX同工型均有表达。
这些实验结果表明，在大鼠肺和外周血管床中，花生四烯酸通过COX-2和COX-1途径转化为血管活性前列腺素，且血栓素A2是正常大鼠肺中形成的主要前列腺素。
