Poore K R, Young I R, Canny B J, Thorburn G D
Department of Physiology, Monash University, Clayton, Victoria 3168, Australia.
Am J Physiol. 1998 Aug;275(2):R357-62. doi: 10.1152/ajpregu.1998.275.2.R357.
Maturation of the fetal adrenal gland is critical for the onset of ovine parturition. It has long been proposed that the fetal adrenal gland may be under inhibitory influences during late gestation. In vitro evidence has suggested that angiotensin II may be such an inhibitory factor and may help to prevent a premature increase in cortisol concentrations. The aim of this study was to test the effect of angiotensin II infusion in vivo on basal cortisol concentrations and fetal adrenal responsiveness to an ACTH-(1-24) challenge. Fetuses received a continuous infusion of either angiotensin II (100 ng . min-1 . kg-1; n = 7) or saline (2 ml/h; n = 4), which commenced at 140 days of gestation (GA) and continued for a total of 50 h. Adrenal responsiveness to the administration of ACTH-(1-24) (5 microg/kg) was determined during angiotensin II or saline infusions at both 2 and 48 h after infusion onset. Angiotensin II had no significant effect on adrenal responsiveness after acute (2 h) or chronic (48 h) infusion. There was no effect of saline or angiotensin II infusion on basal immunoreactive ACTH or cortisol concentrations after 2 h, but there was a significant increase in basal cortisol concentrations in both treatment groups by 48 h, probably reflecting the normal rise in cortisol concentrations at this GA. Mean arterial blood pressure was significantly increased in angiotensin II-infused fetuses only. This study has therefore found no evidence to suggest that angiotensin II infusion in vivo modulates fetal basal cortisol concentrations or adrenal responsiveness in the last week of gestation, in contrast with previous in vitro studies. These results throw into question the proposed role of angiotensin II as a negative modulator of adrenal function in the ovine fetus.
胎儿肾上腺的成熟对于绵羊分娩的开始至关重要。长期以来，人们一直认为胎儿肾上腺在妊娠后期可能受到抑制性影响。体外证据表明，血管紧张素II可能是这样一种抑制因子，可能有助于防止皮质醇浓度过早升高。本研究的目的是测试体内输注血管紧张素II对基础皮质醇浓度以及胎儿肾上腺对促肾上腺皮质激素（1-24）刺激的反应性的影响。胎儿从妊娠140天（GA）开始持续输注血管紧张素II（100 ng·min⁻¹·kg⁻¹；n = 7）或生理盐水（2 ml/h；n = 4），共持续50小时。在输注开始后2小时和48小时的血管紧张素II或生理盐水输注期间，测定肾上腺对促肾上腺皮质激素（1-24）（5 μg/kg）给药的反应性。急性（2小时）或慢性（48小时）输注后，血管紧张素II对肾上腺反应性无显著影响。输注2小时后，生理盐水或血管紧张素II输注对基础免疫反应性促肾上腺皮质激素或皮质醇浓度无影响，但到48小时时，两个治疗组的基础皮质醇浓度均显著升高，这可能反映了在此GA时皮质醇浓度的正常升高。仅在输注血管紧张素II的胎儿中，平均动脉血压显著升高。因此，与先前的体外研究相反，本研究没有发现证据表明体内输注血管紧张素II会在妊娠最后一周调节胎儿基础皮质醇浓度或肾上腺反应性。这些结果对血管紧张素II作为绵羊胎儿肾上腺功能负调节因子的拟议作用提出了质疑。
