Granado M, Amor S, Fernández N, Carreño-Tarragona G, Iglesias-Cruz M C, Martín-Carro B, Monge L, García-Villalón A L
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Nutr Metab Cardiovasc Dis. 2017 Oct;27(10):930-937. doi: 10.1016/j.numecd.2017.06.019. Epub 2017 Jul 8.
The aim of this study was to analyze the effects of early overnutrition (EON) on the expression of the renin angiotensin aldosterone system (RAAS) components in renal cortex, renal arteries and renal perivascular adipose tissue (PVAT), as well as the vascular response of renal arteries to Angiotensin II (Ang II).
On birth day litters were adjusted to twelve (L12-control) or three (L3-overfed) pups per mother. Half of the animals were sacrificed at weaning (21 days old) and the other half at 5 months of age. Ang II-induced vasoconstriction of renal artery segments increased in young overfed rats and decreased in adult overfed rats. EON decreased the gene expression of angiotensinogen (Agt), Ang II receptors AT1 and AT2 and eNOS in renal arteries of young rats, while it increased the mRNA levels of AT-2 and ET-1 in adult rats. In renal PVAT EON up-regulated the gene expression of COX-2 and TNF-α in young rats and the mRNA levels of renin receptor both in young and in adult rats. On the contrary, Ang II receptors mRNA levels were downregulated at both ages. Renal cortex of overfed rats showed increased gene expression of Agt in adult rats and of AT1 in young rats. However the mRNA levels of AT1 were decreased in the renal cortex of overfed adult rats.
EON is associated with alterations in the vascular response of renal arteries to Ang II and changes in the gene expression of RAAS components in renal tissue.
本研究旨在分析早期营养过剩(EON)对肾皮质、肾动脉和肾周血管脂肪组织(PVAT)中肾素血管紧张素醛固酮系统(RAAS)各组分表达的影响,以及肾动脉对血管紧张素II(Ang II)的血管反应。
出生当天,将每窝幼崽调整为每只母鼠哺育12只(L12 - 对照组)或3只(L3 - 过度喂养组)。一半动物在断奶时(21日龄)处死,另一半在5月龄时处死。年轻过度喂养大鼠肾动脉段Ang II诱导的血管收缩增强,成年过度喂养大鼠则减弱。EON降低了年轻大鼠肾动脉中血管紧张素原(Agt)、Ang II受体AT1和AT2以及内皮型一氧化氮合酶(eNOS)的基因表达,而在成年大鼠中它增加了AT - 2和内皮素 - 1(ET - 1)mRNA水平。在肾PVAT中,EON上调了年轻大鼠中环氧合酶 - 2(COX - 2)和肿瘤坏死因子 - α(TNF - α)的基因表达,以及年轻和成年大鼠中肾素受体的mRNA水平。相反,两个年龄段的Ang II受体mRNA水平均下调。过度喂养大鼠的肾皮质在成年大鼠中显示Agt基因表达增加,在年轻大鼠中显示AT1基因表达增加。然而,过度喂养成年大鼠肾皮质中AT1的mRNA水平降低。
EON与肾动脉对Ang II的血管反应改变以及肾组织中RAAS组分的基因表达变化有关。