Wong J, Fineman J R, Heymann M A
Department of Pediatrics, University of California, San Francisco 94143-0544.
Pediatr Res. 1994 Jun;35(6):664-70. doi: 10.1203/00006450-199406000-00008.
The physiologic role of endothelin-1 (ET-1) and its receptors in regulating fetal pulmonary vascular tone is unknown. We therefore investigated the role of ET-1 and its receptors in the regulation of fetal pulmonary vascular tone using BQ 123 (an ETa receptor antagonist) and 4 Ala ET-1 (an ETb receptor agonist). In six fetal sheep in utero, we found that injections of ET-1 (250 ng/kg fetal weight) into the left pulmonary artery increased left pulmonary blood flow (21.0 +/- 17.5 to 74.7 +/- 32.9 mL/kg/min, p < 0.05) and decreased left pulmonary vascular resistance (6.02 +/- 7.00 to 0.84 +/- 0.48 mm Hg/kg/min/mL, p < 0.05). BQ 123 (5 mg) increased pulmonary blood flow (24.6 +/- 28.7 to 47.7 +/- 27.4 mL/kg/min, p < 0.05) and decreased pulmonary vascular resistance (8.84 +/- 10.32 to 1.43 +/- 0.80 mm Hg/kg/min/mL, p < 0.05); 4 Ala ET-1 (1725 ng/kg) markedly increased pulmonary blood flow (8.6 +/- 6.8 to 69.4 +/- 23.1 mL/kg/min, p < 0.05) and decreased pulmonary vascular resistance (12.02 +/- 10.2 to 0.78 +/- 0.44 mm Hg/kg/min/mL, p < 0.05). The absolute increase in pulmonary blood flow produced by ET-1 was attenuated by glibenclamide (an ATP-dependent potassium channel blocker) (flow increase of 73.4 +/- 34.1 versus 49.3 +/- 16.8 mL/kg/min, p < 0.05). This study demonstrates that ETa receptor activation has a small role in maintaining basal fetal pulmonary vascular tone, and that specific ETb receptor activation produces marked pulmonary vasodilation. The increase in pulmonary flow produced by ET-1 in fetuses is partly mediated by ATP-dependent potassium channels.
内皮素 -1（ET -1）及其受体在调节胎儿肺血管张力中的生理作用尚不清楚。因此，我们使用BQ 123（一种ETa受体拮抗剂）和4 Ala ET -1（一种ETb受体激动剂）研究了ET -1及其受体在调节胎儿肺血管张力中的作用。在六只子宫内的胎羊中，我们发现向左肺动脉注射ET -1（250 ng/kg胎儿体重）可增加左肺血流量（从21.0±17.5增至74.7±32.9 mL/kg/min，p<0.05）并降低左肺血管阻力（从6.02±7.00降至0.84±0.48 mmHg/kg/min/mL，p<0.05）。BQ 123（5 mg）可增加肺血流量（从24.6±28.7增至47.7±27.4 mL/kg/min，p<0.05）并降低肺血管阻力（从8.84±10.32降至1.43±0.80 mmHg/kg/min/mL，p<0.05）；4 Ala ET -1（1725 ng/kg）显著增加肺血流量（从8.6±6.8增至69.4±23.1 mL/kg/min，p<0.05）并降低肺血管阻力（从12.02±10.2降至0.78±0.44 mmHg/kg/min/mL，p<0.05）。格列本脲（一种ATP依赖性钾通道阻滞剂）减弱了ET -1引起的肺血流量的绝对增加（血流量增加分别为73.4±34.1与49.3±16.8 mL/kg/min，p<0.05）。本研究表明，ETa受体激活在维持胎儿基础肺血管张力中作用较小，而特定的ETb受体激活可产生显著的肺血管舒张。ET -1在胎儿中引起的肺血流量增加部分由ATP依赖性钾通道介导。
