Fineman J R, Chang R, Soifer S J
Department of Pediatrics, University of California, San Francisco 94143.
Am J Physiol. 1992 May;262(5 Pt 2):H1365-71. doi: 10.1152/ajpheart.1992.262.5.H1365.
There is increasing evidence that resting pulmonary vascular tone is mediated by the release of endothelium-derived relaxing factors (EDRF). However, the importance of EDRF release during pulmonary hypertension is unknown. Therefore, in eight newborn lambs we studied the effects of both N omega-nitro-L-arginine (an inhibitor of EDRF synthesis) and L-arginine (a precursor of EDRF synthesis) during pulmonary hypertension induced either by the intravenous infusion of U-46619 (a thromboxane A2 mimic) or by hypoxia. After pretreatment with N omega-nitro-L-arginine, the increases in pulmonary arterial pressure produced by U-46619 (102.0 +/- 34.9% vs. 144.8 +/- 28.6%, P less than 0.05) and by hypoxia (35.6 +/- 17.3% vs. 91.4 +/- 24.8%, P less than 0.05) were significantly augmented. However, after pretreatment with L-arginine, the increases in pulmonary arterial pressure produced by U-46619 (107.0 +/- 21.4% vs. 62.6 +/- 22.6%, P less than 0.05) and hypoxia (44.3 +/- 18.3% vs. 9.2 +/- 11.7%, P less than 0.05) were significantly attenuated. These results suggest that during pulmonary hypertension, EDRF is released to limit the increase in pulmonary arterial pressure and that L-arginine availability becomes rate limiting for further EDRF synthesis and release.
越来越多的证据表明，静息肺血管张力是由内皮衍生舒张因子（EDRF）的释放介导的。然而，肺动脉高压期间EDRF释放的重要性尚不清楚。因此，我们在八只新生羔羊中研究了Nω-硝基-L-精氨酸（一种EDRF合成抑制剂）和L-精氨酸（一种EDRF合成前体）在通过静脉输注U-46619（一种血栓素A2类似物）或缺氧诱导的肺动脉高压期间的作用。用Nω-硝基-L-精氨酸预处理后，U-46619（102.0±34.9%对144.8±28.6%，P<0.05）和缺氧（35.6±17.3%对91.4±24.8%，P<0.05）引起的肺动脉压升高显著增强。然而，用L-精氨酸预处理后，U-46619（107.0±21.4%对62.6±22.6%，P<0.05）和缺氧（44.3±18.3%对9.2±11.7%，P<0.05）引起的肺动脉压升高显著减弱。这些结果表明，在肺动脉高压期间，EDRF被释放以限制肺动脉压的升高，并且L-精氨酸的可用性成为进一步EDRF合成和释放的限速因素。
