Ohara Maiko, Tomoda Fumihiro, Koike Tsutomu, Liu Hexing, Uno Kyosuke, Nitta Atsumi, Inoue Hiroshi
The Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
The Department of Pharmaceutical Therapy and Neuropharmacology, University of Toyama, Toyama, Japan.
Clin Exp Pharmacol Physiol. 2015 Jun;42(6):687-94. doi: 10.1111/1440-1681.12411.
To investigate the role of nerve growth factor (NGF) in the development of hypertensive renal vascular remodeling, antiserum against NGF (anti-NGF) or vehicle was injected at 3 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each treatment in each strain). Flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships at vasodilated perfused kidneys were determined at 10 weeks of age. In the vehicle rats, blood pressure, renal noradrenaline content, the gradient of F-P (minimal vascular resistance at pre- and post-glomerular vasculature) and the X-intercept of P-GFR (preglomerular : postglomerular vascular resistance ratio) were greater in SHR than in WKY rats, although the gradient of P-GFR (glomerular filtration capacity) did not differ significantly between the strains. Blood pressure and renal noradrenaline content were lower in SHR receiving anti-NGF than in SHR receiving vehicle, although such difference was not observed in WKY rats. The gradient of F-P was less but the gradient of P-GFR was greater in SHR receiving anti-NGF compared with SHR receiving vehicle, although the similar differences did not occur in WKY rats. Blood pressure and renal noradrenaline content remained greater in SHR treated with anti-NGF compared with WKY rats treated with vehicle; however, the gradient of F-P did not differ significantly between them. Contrary, anti-NGF did not affect the X-intercept of P-GFR in either strain. In conclusion, NGF could contribute to the genesis of renal vascular remodeling, at least in part, through modification of renal sympathetic activity and blood pressure in SHR.
为研究神经生长因子（NGF）在高血压性肾血管重塑发展中的作用，于3周龄时向自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠体内注射抗NGF抗血清（anti-NGF）或赋形剂（每种品系的每种处理n = 9）。在10周龄时测定血管舒张灌注肾的血流-压力（F-P）和压力-肾小球滤过率（P-GFR）关系。在赋形剂处理的大鼠中，SHR的血压、肾去甲肾上腺素含量、F-P梯度（肾小球前和肾小球后血管系统的最小血管阻力）以及P-GFR的X截距（肾小球前：肾小球后血管阻力比）均高于WKY大鼠，尽管两品系之间P-GFR梯度（肾小球滤过能力）无显著差异。接受anti-NGF的SHR的血压和肾去甲肾上腺素含量低于接受赋形剂的SHR，尽管在WKY大鼠中未观察到这种差异。与接受赋形剂的SHR相比，接受anti-NGF的SHR的F-P梯度较小，但P-GFR梯度较大，尽管在WKY大鼠中未出现类似差异。与接受赋形剂处理的WKY大鼠相比，接受anti-NGF处理的SHR的血压和肾去甲肾上腺素含量仍然较高；然而，它们之间的F-P梯度无显著差异。相反，anti-NGF对任一品系的P-GFR的X截距均无影响。总之，NGF至少部分地通过改变SHR的肾交感神经活性和血压，促进肾血管重塑的发生。
