Guanylyl Cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia Models
Guanylyl Cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia Models
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肾近端肾小管和血管内皮细胞中的鸟苷酸环化酶 A 可保护啮齿动物实验性内毒素血症模型中的肾脏免受急性损伤
作者：
Hiroaki Kitamura;D. Nakano;Yoshiharu Sawanobori;Takehiko Asaga;H. Yokoi;M. Yanagita;M. Mukoyama;T. Tokudome;K. Kangawa;G. Shirakami;A. Nishiyama
关于这个话题我们已经知道的是钠尿肽的生理作用在危重疾病中被越来越多地了解，但这些肽如何可能影响败血症引起的少尿尚不清楚本文告诉我们的是，在一项实验性脓毒症的体内研究中，液体复苏恢复了肾小球滤过，但重组心房利钠肽恢复了肾小管血流和肾小球滤过背景：根据经验观察，利钠肽在重症监护病房用作抗低尿治疗。我们假设利钠肽通过激活近端小管和血管内皮细胞上的尿钠素受体鸟苷酸环化酶A来预防脂多糖诱导的少尿。方法：用脂多糖刺激内皮细胞和近端肾小管上皮细胞鸟苷酸环化酶A缺失的正常SD大鼠和小鼠，用多光子显微镜活体显像法检测少尿和肾小管内流量。结果：重组心钠素能在不改变血压的情况下有效地增加大鼠内毒素攻击后的尿量(4 h尿量，脂多糖：0.6 ± 0.3 ml·kg−1·h−1；脂多糖+液体复苏：4.6 ± 2.0 ml·kg−1·h−1；脂多糖+液体复苏+心钠素：9.0 ± 4.8 ml·kg−1·h−1；平均±SD；n=5)。活体成像显示，脂多糖降低了肾小球滤过率，减慢了近端肾小管的血流速度。液体复苏可恢复肾小球滤过率，但不能恢复肾小管流量。在液体复苏中加入心钠素可改善肾小球滤过率和肾小管流量。与对照组相比，近端小管或血管内皮细胞缺乏鸟苷酸环化酶A的小鼠在心钠素治疗后肾小管流量的改善较小。内皮细胞，而不是近端小管，鸟苷酸环化酶A的缺失增加了内毒素对肾小球滤过率的降低。结论：内源性和外源性利钠肽均可通过激活近曲小管和内皮细胞的鸟苷酸环化酶A来预防内毒素诱导的少尿。
What We Already Know about This TopicThe physiologic role of natriuretic peptides is increasingly understood in critical illness, but how these peptides might impact sepsis-induced oliguria is not known What This Article Tells Us That Is NewIn an in vivo study of experimental sepsis, fluid resuscitation restored glomerular filtration, but recombinant atrial natriuretic peptide restored renal tubular flow and glomerular filtration Background: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. Methods: Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy. Results: Recombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg−1 · h−1; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg−1 · h−1; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg−1 · h−1; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide. Conclusions: Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.
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DOI：
10.1152/ajplung.00202.2009
发表时间：
2010-11-01
影响因子：
4.9
作者：
Birukova, Anna A.;Xing, Junjie;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.
atriopeptin III 对离体大鼠传入和传出小动脉的影响。
DOI：
10.1152/ajprenal.1991.261.6.f1102
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
Lanese,DM;Yuan,BH;Falk,SA;Conger,JD
通讯作者：
Conger,JD
影响因子：
15.9
作者：
Tran, Mei;Tam, Denise;Parikh, Samir M.
通讯作者：
Parikh, Samir M.
ANP 受体在 LPS 诱导的内皮通透性减弱和肺损伤中发挥相反作用。
影响因子：
3.1
作者：
Xing,Junjie;Yakubov,Bakhtiyor;Poroyko,Valeriy;Birukova,AnnaA
通讯作者：
Birukova,AnnaA
DOI：
10.1152/ajprenal.00638.2012
发表时间：
2013-04-01
影响因子：
4.2
作者：
Guo, Lai-Jing;Alli, Abdel A.;Bao, Hui-Fang
通讯作者：
Bao, Hui-Fang