Extravascular renal denervation ameliorates juvenile hypertension and renal damage resulting from experimental hyperleptinemia in rats
Extravascular renal denervation ameliorates juvenile hypertension and renal damage resulting from experimental hyperleptinemia in rats
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DOI：
10.1097/hjh.0000000000001472
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发表时间：
2017-12-01
影响因子：
4.9
通讯作者：
Samuelsson, Anne-Maj
中科院分区：
文献类型：
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作者：
Oosterhuis, Nynke R.;Fernandes, Ramon;Samuelsson, Anne-Maj
背景：啮齿类动物的实质性肥胖与新生儿高瘦素血症和成年后代的交感神经源性高血压有关。以前，我们报道了实验诱导的高瘦素血症在大鼠幼鼠的结果在成年期高血压。在这里，我们解决的假设，实验性新生儿高瘦素血症，通过肾神经激活，不利地影响成人renal function.Method：Sprague-Dawley雄性和雌性幼仔进行了治疗与新生儿瘦素（3 mg/kg，腹膜内）或新生儿生理盐水，每天两次，从出生后第9-14天。幼年（1个月）新生瘦素和新生盐水大鼠进行双侧肾去神经，单侧肾去神经或假手术。结果：未成年新生瘦素大鼠肾神经完整，平均动脉压（MAP）升高，伴有局部肾素-血管紧张素系统过度活跃，肾小球滤过率降低。双侧肾脏去神经保护大鼠免受新生儿瘦素诱导的MAP，肾脏肾素-血管紧张素系统和肾小球滤过率受损。交感神经介导的肾小管间质损伤的年轻成年（2个月）新生儿瘦素女性的两倍增加，抑制单侧肾去神经支配，独立的MAP。新生瘦素大鼠也表现出尿蛋白，中性粒细胞明胶酶相关脂质运载蛋白，肾损伤分子-1的增加。血压升高与盐敏感性增加和持续的肾功能不全adult.Conclusion：我们建议，新生儿高瘦素血症方案长期肾结构和功能的损害，通过肾交感神经激活。
Background:Material obesity in rodents is associated with neonatal hyperleptinemia and hypertension of sympathetic origin in adult offspring. Previously, we reported that experimentally induced hyperleptinemia in rat pups results in adulthood hypertension. Here, we addressed the hypothesis that experimental neonatal hyperleptinemia, through renal nerve activation, adversely affects adult renal function.Method:Sprague-Dawley male and female pups were treated with neonatal leptin (3mg/kg, intraperitoneal) or neonatal saline, twice daily from postnatal day 9-14. Juvenile (1 month) neonatal leptin and neonatal saline rats were subjected to either bilateral renal denervation, unilateral renal denervation or Sham surgery. Arterial pressure was telemetrically monitored.Results:Juvenile neonatal leptin rats with intact renal nerves demonstrated increased mean arterial pressure (MAP) accompanied by local renin-angiotensin system overactivity and reduced glomerular filtration rate. Bilateral renal denervation in rats protected against neonatal leptin-induced MAP, renal renin-angiotensin system and impaired glomerular filtration rate. A two-fold increase in sympathetically mediated tubulointerstitial damage in young adult (2 months) neonatal leptin females, was suppressed by unilateral renal denervation, independent of MAP. Neonatal leptin rats also demonstrated increases in urinary protein, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Raised blood pressure was associated with increased salt sensitivity and with sustained renal dysfunction in adulthood.Conclusion:We propose that neonatal hyperleptinemia programmes long-term renal structural and functional damage, through renal sympathetic nerve activation.