血管紧张素II受体阻断及其对人体肺血流动力学和低氧性肺血管收缩的影响。

Angiotensin II receptor blockade and effects on pulmonary hemodynamics and hypoxic pulmonary vasoconstriction in humans.

作者信息

Kiely D G, Cargill R I, Lipworth B J

机构信息

Department of Clinical Pharmacology, Ninewells Hospital, Dundee, Scotland.

出版信息

Chest. 1996 Sep;110(3):698-703. doi: 10.1378/chest.110.3.698.

DOI:10.1378/chest.110.3.698

PMID:8797414

Abstract

STUDY OBJECTIVE

We examined the hypothesis that angiotensin II (ANG II) is a modulator of pulmonary vascular tone by examining the effects of ANG II blockade on pulmonary hemodynamics during normoxemia and hypoxemia in normal volunteers with an activated renin angiotensin system (RAS).

PARTICIPANTS AND INTERVENTIONS

Eight normal volunteers, pretreated with furosemide, were studied on two separate occasions and received either an infusion of saralasin, 5 micrograms/kg/min, or placebo. After 20 min, they were rendered hypoxemic, by breathing N2/O2 mixture for 20 min to achieve arterial oxygen saturation (SaO2) of 85 to 90% adjusted for a further 20 min to achieve SaO2 of 75 to 80%. Doppler echocardiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output, and hence total pulmonary vascular resistance (TPR).

RESULTS

Saralasin compared with placebo resulted in a significant (p < 0.05) reduction in MPAP during normoxemia, 6.70 +/- 1.0 vs 11.7 +/- 1.3 mm Hg; at SaO2 of 85 to 90%, 14.7 +/- 1.4 vs 20.5 +/- 1.0 mm Hg; and at SaO2 of 75 to 80%, 18.1 +/- 1.9 vs 27.8 +/- 1.9 mm Hg, respectively. Likewise saralasin compared with placebo resulted in a significant reduction in TPR during normoxemia, 104 +/- 14 vs 180 +/- 20 dyne.s.cm-5; at SaO2 of 85 to 90%, 222 +/- 24 vs 295 +/- 21 dyne.s.cm-5; and at SaO2 of 75 to 80%, 238 +/- 21 vs 362 +/- 11 dyne.s.cm-5, respectively. The delta MPAP response to hypoxemia was likewise significantly (p < 0.01) attenuated by saralasin infusion compared with placebo: mean difference 5.0 mm Hg, 95% confidence interval (CI) 1.9 to 8.08, and there was a trend toward attenuation of the delta TPR response to hypoxemia (0.05 < p < 0.10): mean difference 47 dyne.s.cm-5, 95% CI, -10 to 105.

CONCLUSION

In addition to causing pulmonary vasodilatation in the presence of an activated RAS, our results suggest that ANG II receptor blockade attenuates acute hypoxic pulmonary vasoconstriction and that ANG II may play a role in modulating this response in normal man.

摘要

研究目的

我们通过研究在肾素 - 血管紧张素系统（RAS）激活的正常志愿者中，血管紧张素II（ANG II）阻断对常氧血症和低氧血症期间肺血流动力学的影响，来检验ANG II是肺血管张力调节因子这一假设。

参与者与干预措施

8名预先用速尿治疗的正常志愿者在两个不同时段接受研究，分别输注沙拉新（5微克/千克/分钟）或安慰剂。20分钟后，通过吸入N₂/O₂混合气体20分钟使他们处于低氧血症状态，将动脉血氧饱和度（SaO₂）调整至85%至90%，再持续20分钟将SaO₂调整至75%至80%。使用多普勒超声心动图测量平均肺动脉压（MPAP）、心输出量，进而计算总肺血管阻力（TPR）。

结果

与安慰剂相比，沙拉新使常氧血症时的MPAP显著降低（p < 0.05），分别为6.70±1.0 vs 11.7±1.3 mmHg；在SaO₂为85%至90%时，分别为14.7±1.4 vs 20.5±1.0 mmHg；在SaO₂为75%至80%时，分别为18.1±1.9 vs 27.8±1.9 mmHg。同样，与安慰剂相比，沙拉新使常氧血症时的TPR显著降低，分别为104±14 vs 180±20达因·秒·厘米⁻⁵；在SaO₂为85%至90%时，分别为22,2±24 vs 295±21达因·秒·厘米⁻⁵；在SaO₂为75%至80%时，分别为238±21 vs 362±11达因·秒·厘米⁻⁵。与安慰剂相比，输注沙拉新同样使低氧血症时MPAP的变化显著减弱（p < 0.01）：平均差值5.0 mmHg，95%置信区间（CI）1.9至8.08，并且低氧血症时TPR变化有减弱趋势（0.05 < p < 0.10）：平均差值47达因·秒·厘米⁻⁵，95% CI， -10至105。