Shi Lijun, Yao Jiaming, Koos Brian J, Xu Zhice
Harbor-Ucla Research Institute, Torrance, CA, USA.
Brain Res Dev Brain Res. 2004 Oct 15;153(1):53-60. doi: 10.1016/j.devbrainres.2004.07.012.
Previous fetal studies have indicated depressor responses of intravenous (i.v.) administration of angiotensin antagonists. However, little is known of central effects of angiotensin blockers on fetal cardiovascular controlling. The cardiovascular effects of central administration of the angiotensin-1 (AT(1)) and angiotensin-2 (AT(2)) receptor antagonists, losartan and PD123319, were investigated in the chronically catheterized near-term ovine fetuses. Intravenous losartan produced within 1.5 min a significant and persistent depressor response [maximum Delta mean arterial pressure (MAP)=9 mm Hg] without altering fetal heart rate. Intracerebroventricular (i.c.v.) administration of losartan (1-5 mg/kg) increased fetal arterial pressures (Delta MAP=9-14 mm Hg). Central application of losartan (1 mg/kg) also increased fetal heart rate (maximum Delta heart rate=33 beat per minute). Losartan increased c-fos expression in the median preoptic nucleus and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, the lateral parabrachial nuclei, and the ventrolateral medullabrain. These brain sectors are with abundant AT(1) receptors and have been demonstrated in the involvement in cardiovascular regulation. In contrast, intracerebroventricular injection of the AT(2) receptor antagonist PD123319 had no effect on fetal arterial pressure and heart rate. The results demonstrate strikingly functional differences of losartan on the fetal cardiovascular regulation in central and peripheral sides.
先前的胎儿研究表明，静脉注射血管紧张素拮抗剂会产生降压反应。然而，关于血管紧张素阻滞剂对胎儿心血管控制的中枢作用却知之甚少。我们在长期插管的近足月绵羊胎儿中研究了中枢给予血管紧张素1（AT(1)）受体拮抗剂氯沙坦和血管紧张素2（AT(2)）受体拮抗剂PD123319对心血管的影响。静脉注射氯沙坦在1.5分钟内产生显著且持续的降压反应[平均动脉压（MAP）最大变化量=9毫米汞柱]，且不改变胎儿心率。脑室内注射氯沙坦（1 - 5毫克/千克）可使胎儿动脉压升高（MAP变化量=9 - 14毫米汞柱）。中枢给予氯沙坦（1毫克/千克）还可使胎儿心率增加（心率最大变化量=每分钟33次）。氯沙坦增加了前脑视前正中核和室旁核以及孤束核、外侧臂旁核和延髓腹外侧脑区的c - fos表达。这些脑区有丰富的AT(1)受体，且已被证明参与心血管调节。相比之下，脑室内注射AT(2)受体拮抗剂PD123319对胎儿动脉压和心率没有影响。结果表明，氯沙坦在胎儿心血管调节的中枢和外周方面存在显著的功能差异。
