Abstract:
A solitary functioning kidney (SFK) from birth predisposes to hypertension and kidney dysfunction, and this may be associated with impaired fluid and sodium homeostasis. Brief and early angiotensin-converting enzyme inhibition (ACEi) in a sheep model of SFK delays onset of kidney dysfunction. We hypothesized that modulation of the renin-angiotensin system via brief postnatal ACEi in SFK would reprogram renal sodium and water handling. Here, blood pressure (BP), kidney haemodynamics and kidney excretory function were examined in response to an isotonic saline load (0.13 ml/kg/min, 180 min) at 20 months of age in SFK (fetal unilateral nephrectomy at 100 days gestation; term 150 days), sham and SFK+ACEi sheep (ACEi in SFK 4-8 weeks of age). Basal BP was higher in SFK than sham (∼13 mmHg), and similar between SFK and SFK+ACEi groups. Saline loading caused a small increase in BP (∼3-4 mmHg) the first 2 h in SFK and sham sheep but not SFK+ACEi sheep. Glomerular filtration rate did not change in response to saline loading. Total sodium excretion was similar between groups. Total urine excretion was similar between SFK and sham animals but was ∼40% less in SFK+ACEi animals compared with SFK animals. In conclusion, the present study indicates that water homeostasis in response to a physiological challenge is attenuated at 20 months of age by brief early life ACEi in SFK. Further studies are required to determine if ACEi in early life in children with SFK could compromise fluid homeostasis later in life.
摘要:
一个单独的功能肾脏(SFK)从出生易患高血压和肾功能不全,这可能与受损的体液和钠稳态有关。绵羊SFK模型中的短暂和早期血管紧张素转换酶抑制(ACEi)可延迟肾功能障碍的发作。我们假设通过SFK中短暂的出生后ACEi调节肾素血管紧张素系统会重新编程肾钠和水的处理。这里,血压(BP),在20个月大的SFK(妊娠100天的胎儿单侧肾切除术;足月150天)中,响应于等渗盐水负荷(0.13ml/kg/min;180分钟)检查肾脏血流动力学和肾脏排泄功能,假和SFK+ACEi绵羊(ACEi在SFK4-8周龄)。SFK的基础血压高于假手术(13mmHg),SFK和SFK+ACEi组之间相似。盐水负荷在前两个小时内引起SFK和假绵羊而不是SFKACEi绵羊的BP(3-4mmHg)小幅增加。肾小球滤过率没有响应于盐水负荷而改变。两组之间的总钠排泄相似。SFK和假动物之间的总尿液排泄相似,但与SFK动物相比,SFK+ACEi动物的总尿液排泄减少了40%。总之,这项研究表明,在SFK中,短暂的早期生活ACEi在20个月大时减轻了对生理挑战的反应的水稳态。需要进一步的研究来确定SFK儿童早期的ACEi是否会在以后的生活中损害体液稳态。