Sanhueza Emilia M, Johansen-Bibby Anja A, Fletcher Andrew J W, Riquelme Raquel A, Daniels Alejandro J, Serón-Ferré Maria, Gaete Cristián R, Carrasco Jorge E, Llanos Aníbal J, Giussani Dino A
Programa de Fisiopatología, Instituto de Ciencias Biomédicas (ICMB), Facultad de Medicina and Centro Internacional de Estudios Andinos (INCAS), Universidad de Chile, Chile.
J Physiol. 2003 Feb 1;546(Pt 3):891-901. doi: 10.1113/jphysiol.2002.034488.
This study investigated the role of neuropeptide Y (NPY) in mediating cardiovascular responses to reduced oxygenation in the late gestation ovine fetus by: (1) comparing the effects on the cardiovascular system of an exogenous infusion of NPY with those elicited by moderate or severe reductions in fetal oxygenation; and (2) determining the effect of fetal I.V. treatment with a selective NPY-Y(1) receptor antagonist on the fetal cardiovascular responses to acute moderate hypoxaemia. Under general anaesthesia, 14 sheep fetuses (0.8-0.9 of gestation) were surgically prepared with vascular and amniotic catheters. In 5 of these fetuses, a Transonic flow probe was also implanted around a femoral artery. Following at least 5 days of recovery, one group of fetuses (n = 9) was subjected to a 30 min treatment period with exogenous NPY (17 microg kg(-1) bolus plus 0.85 microg kg(-1) min(-1) infusion). In this group, fetal blood pressure and heart rate were monitored continuously and the distribution of the fetal combined ventricular output was assessed via injection of radiolabelled microspheres before and during treatment. The second group of fetuses instrumented with the femoral flow probe (n = 5) were subjected to a 3 h experiment consisting of 1 h of normoxia, 1 h of hypoxaemia, and 1 h of recovery during a slow I.V. infusion of vehicle. One or two days later, the acute hypoxaemia protocol was repeated during fetal I.V. treatment with a selective NPY-Y(1) receptor antagonist (50 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion). In these fetuses, fetal arterial blood pressure, heart rate and femoral vascular resistance were recorded continuously. The results show that fetal treatment with exogenous NPY mimics the fetal cardiovascular responses to asphyxia, and that treatment of the sheep fetus with a selective NPY-Y(1) receptor antagonist does not affect the fetal cardiovascular response to acute moderate hypoxaemia. These results support a greater role for NPY in mediating the fetal cardiovascular responses to acute asphyxia than to acute moderate hypoxaemia.
本研究通过以下方式探究了神经肽Y（NPY）在介导妊娠晚期绵羊胎儿对氧合降低的心血管反应中的作用：（1）比较外源性输注NPY对心血管系统的影响与胎儿氧合中度或严重降低所引发的影响；（2）确定胎儿静脉注射选择性NPY-Y(1)受体拮抗剂对胎儿心血管对急性中度低氧血症反应的影响。在全身麻醉下，对14只绵羊胎儿（妊娠0.8 - 0.9期）进行手术，植入血管和羊膜导管。在其中5只胎儿中，还在股动脉周围植入了Transonic血流探头。在至少5天的恢复后，一组胎儿（n = 9）接受30分钟的外源性NPY治疗（17μg kg(-1)推注加0.85μg kg(-1) min(-1)输注）。在该组中，连续监测胎儿血压和心率，并在治疗前和治疗期间通过注射放射性微球评估胎儿联合心室输出的分布。第二组植入股动脉血流探头的胎儿（n = 5）进行了一项3小时的实验，包括1小时的常氧、1小时的低氧血症以及在缓慢静脉输注载体期间1小时的恢复。1或2天后，在胎儿静脉注射选择性NPY-Y(1)受体拮抗剂（50μg kg(-1)推注 + 1.5μg kg(-1) min(-1)输注）期间重复急性低氧血症方案。在这些胎儿中，连续记录胎儿动脉血压、心率和股血管阻力。结果表明，用外源性NPY治疗胎儿可模拟胎儿对窒息的心血管反应，并且用选择性NPY-Y(1)受体拮抗剂治疗绵羊胎儿不会影响胎儿对急性中度低氧血症的心血管反应。这些结果支持NPY在介导胎儿对急性窒息的心血管反应中比在介导对急性中度低氧血症的反应中发挥更大作用。
