Combined thyroidectomy and renal denervation suppress renin expression and secretion in fetal sheep.

Kai Chen, Luke C Carey, Nancy K Valego, Jingfang Liu, James C Rose
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引用次数: 1

Abstract

Background and objectives: Activity of the fetal renin-angiotensin system (RAS) is developmentally regulated, increasing in late gestation toward term. Thyroid hormone and the renal nerves are both important modulators of renal RAS maturation; however, ablation of either influence alone does not totally block the aforementioned developmental late gestation increase in RAS in fetal sheep. In the current study, we used the technique of thyroidectomy combined with bilateral renal denervation (TX+D), which removes thyroid hormone from the circulation and abolishes effects of renal nerve activity, to determine if simultaneous removal of their effects on the kidney would markedly alter renin expression and secretion in late gestation.

Methods: TX+D was performed at 120 days of gestation age (dGA). Control fetuses were sham-operated. Immediately before necropsy (approximately 138 dGA), fetuses were infused with isoproterenol to examine plasma active and prorenin changes in response to beta-adrenergic stimulation.

Results: TX+D decreased plasma thyroid hormone concentrations, renal renin mRNA, renal active and prorenin levels, and plasma active and prorenin concentrations. Isoproterenol-induced increases in plasma active renin were also reduced in TX+D fetuses. TX+D did not alter renal angiotensin (Ang) II subtype receptor (AT2) expression close to term.

Conclusion: These findings suggest that TX+D synergize in the suppression of fetal renin expression.

甲状腺切除联合肾去神经抑制胎羊肾素的表达和分泌。
背景和目的:胎儿肾素-血管紧张素系统(RAS)的活性受发育调控,在妊娠晚期至足月增加。甲状腺激素和肾神经都是肾RAS成熟的重要调节因子;然而,单独消除任何一种影响并不能完全阻断胎羊妊娠后期RAS的上述发育性增加。在本研究中,我们采用甲状腺切除术联合双侧肾去神经支配(TX+D)技术,将甲状腺激素从循环中去除,并消除肾神经活动的影响,以确定同时去除它们对肾脏的影响是否会显著改变妊娠后期肾素的表达和分泌。方法:在孕龄120天(dGA)进行TX+D。对照组胎儿进行假手术。在尸检前(大约138胎龄),胎儿被注入异丙肾上腺素,以检测血浆活性和prorenin对-肾上腺素能刺激的反应。结果:TX+D降低血浆甲状腺激素浓度、肾肾素mRNA、肾活性和前肾素水平以及血浆活性和前肾素浓度。异丙肾上腺素引起的血浆活性肾素升高在TX+D胎儿中也有所降低。接近足月时,TX+D未改变肾血管紧张素(Ang) II亚型受体(AT2)的表达。结论:TX+D可协同抑制胎儿肾素的表达。
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