Zellers T M, Wu Y Q, McCormick J, Vanhoutte P M
Department of Pediatrics, Division of Cardiology University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.
Acta Pharmacol Sin. 2000 Feb;21(2):131-8.
To study the interactions between prostacyclin and endothelium-derived nitric oxide in porcine pulmonary arteries.
Rings of 5th order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides.
Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phenylephrine contraction) that were inhibited by the inhibitors of the L-arginine nitric oxide pathway, oxyhemoglobin and N omega-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach statistical significance compared to controls. The addition of 8-bromo-cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-L-arginine (NLA), reduced the prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin-induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium.
These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by basally released endothelium-derived nitric oxide.
研究前列环素与内皮源性一氧化氮在猪肺动脉中的相互作用。
对猪肺动脉第5级血管环进行体外研究，以测量张力和环核苷酸含量。
外源性给予前列环素可引起内皮依赖性舒张（抑制去氧肾上腺素收缩），该舒张作用被L-精氨酸一氧化氮途径抑制剂、氧合血红蛋白和Nω-硝基-L-精氨酸抑制。这些抑制剂对无内皮血管环的张力无影响。在前列环素存在下，环鸟苷酸浓度未高于基础浓度。乙酰胆碱和硝普钠可使其升高。与对照组相比，前列环素刺激的环腺苷酸浓度未达到统计学显著差异。然而，向前列环素中添加8-溴环鸟苷酸可增加环腺苷酸含量。一氧化氮合酶抑制剂硝基-L-精氨酸（NLA）可将前列环素刺激的环腺苷酸含量降至基础水平。8-溴环鸟苷酸或氨力农（该酶的特异性抑制剂）抑制环鸟苷酸抑制的环腺苷酸磷酸二酯酶，可使无内皮血管环中前列环素诱导的舒张增强至与有内皮血管环中观察到的幅度相似。
这些数据表明，内皮对前列环素诱导的猪肺动脉舒张的增强作用是由于基础释放的内皮源性一氧化氮抑制了环鸟苷酸抑制的环腺苷酸磷酸二酯酶所致。
