Wang Tao, Kobayashi Yuta, Nabika Toru, Takabatake Toshikazu
The Fourth Department of Internal Medicine, Shimane University School of Medicine, Izumo, Japan.
Clin Exp Pharmacol Physiol. 2005 Dec;32(12):1055-60. doi: 10.1111/j.1440-1681.2005.04304.x.
Recent studies suggest that a quantitative trait locus (QTL) for blood pressure (BP) on rat chromosome 1 is associated with exaggerated sympathetic nervous activity. The aim of the present study was to examine whether this QTL can affect BP by altering sympathetic control of renal function. Male stroke-prone spontaneously hypertensive rats of Izumo origin (SHRSP/Izm), Wistar-Kyoto rats (WKY/Izm) and rats from a WKY/Izm congenic strain that contains an SHRSP/Izm chromosomal segment between D1Wox29 and D1Arb21 (WKYpch1.0) were used. Clearance and micropuncture experiments were performed in anaesthetized rats after acute unilateral renal denervation (DN). Mean BP in sham-operated WKYpch1.0 was significantly higher than that in WKY/Izm. The DN procedure elicited a greater reduction in renal noradrenaline levels in SHRSP/Izm and WKYpch1.0 than in WKY/Izm. In both SHRSP/Izm and WKYpch1.0, DN decreased renal vascular resistance and filtration fraction, whereas it increased renal blood flow and urinary and fractional excretion of sodium. Unilateral renal denervation did not affect these parameters in WKY/Izm. Unilateral renal denervation decreased the tubuloglomerular feedback (TGF) responsiveness only in SHRSP/Izm, whereas it increased the non-perfused early proximal flow rate in SHRSP/Izm and WKYpch1.0. The results of the present study indicate that the renal sympathetic nervous system exerts enhanced tonic control of the renal vasculature and tubular function in SHRSP/Izm and WKYpch1.0, but not in WKY/Izm. Neural impact on the TGF response in WKYpch1.0 is indiscernible. Thus, a gene or genes in the QTL may influence BP, at least in part, through renal vasoconstriction and sodium retention mediated by the enhanced activity of the renal sympathetic nerves.
最近的研究表明，大鼠1号染色体上的一个血压（BP）数量性状基因座（QTL）与交感神经活动亢进有关。本研究的目的是检验该QTL是否可通过改变对肾功能的交感神经控制来影响血压。使用了泉涌源的雄性易卒中型自发性高血压大鼠（SHRSP/Izm）、Wistar-Kyoto大鼠（WKY/Izm）以及来自WKY/Izm同基因品系的大鼠，该品系在D1Wox29和D1Arb21之间包含一个SHRSP/Izm染色体片段（WKYpch1.0）。在急性单侧肾去神经支配（DN）后，对麻醉大鼠进行清除率和微穿刺实验。假手术的WKYpch1.0大鼠的平均血压显著高于WKY/Izm大鼠。与WKY/Izm相比，DN程序在SHRSP/Izm和WKYpch1.0中引起肾去甲肾上腺素水平更大幅度的降低。在SHRSP/Izm和WKYpch1.0中，DN均降低了肾血管阻力和滤过分数，而增加了肾血流量以及尿钠排泄和钠分数排泄。单侧肾去神经支配对WKY/Izm的这些参数没有影响。单侧肾去神经支配仅在SHRSP/Izm中降低了肾小管-肾小球反馈（TGF）反应性，而在SHRSP/Izm和WKYpch1.0中增加了未灌注的早期近端流速。本研究结果表明，肾交感神经系统对SHRSP/Izm和WKYpch1.0中的肾血管系统和肾小管功能施加了增强的紧张性控制，但对WKY/Izm没有。WKYpch1.0中神经对TGF反应的影响难以察觉。因此，该QTL中的一个或多个基因可能至少部分地通过肾交感神经增强的活性介导的肾血管收缩和钠潴留来影响血压。
