Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC 20007, USA.
Hypertension. 2010 Apr;55(4):983-9. doi: 10.1161/HYPERTENSIONAHA.109.149120. Epub 2010 Mar 1.
Because defects in renal autoregulation may contribute to renal barotrauma in chronic kidney disease, we tested the hypothesis that the myogenic response is diminished by reduced renal mass. Kidneys from 5/6 nephrectomized mice had only a minor increase in the glomerular sclerosis index. The telemetric mean arterial pressure (108+/-10 mm Hg) was unaffected after 3 months of high-salt intake (6% salt in chow) or reduced renal mass. Afferent arterioles from 5/6 nephrectomized mice and sham-operated controls were perfused ex vivo during step changes in pressure from 40 to 134 mm Hg. Afferent arterioles developed a constriction and a linear increase in active wall tension above a perfusion pressure of 36+/-6 mm Hg, without a plateau. The slope of active wall tension versus perfusion pressure defined the myogenic response, which was similar in sham mice fed normal or high-salt diets for 3 months (2.90+/-0.22 versus 3.22+/-0.40 dynes x cm(-1)/mm Hg; P value not significant). The myogenic response was unaffected after 3 days of reduced renal mass on either salt diet (3.39+/-0.61 versus 4.04+/-0.47 dynes x cm(-1)/mm Hg) but was reduced (P<0.05) in afferent arterioles from reduced renal mass groups fed normal and high salt at 3 months (2.10+/-0.28 and 1.35+/-0.21 dynes x cm(-1)/mm Hg). In conclusion, mouse renal afferent arterioles develop a linear increase in myogenic tone around the range of ambient perfusion pressures. This myogenic response is impaired substantially in the mouse model of prolonged reduced renal mass, especially during high salt intake.
由于肾脏自身调节功能的缺陷可能导致慢性肾脏病中的肾气压伤，我们检验了如下假说：肾单位减少会导致肌源性反应减弱。5/6 肾切除的小鼠肾小球硬化指数仅有轻微升高。3 个月高盐饮食（饲料中盐含量 6%）或肾单位减少后，可测量平均动脉压（108+/-10mmHg）无变化。5/6 肾切除的和假手术对照组的小鼠离体在压力从 40mmHg 到 134mmHg 的阶跃变化下，其入球小动脉被灌流。入球小动脉在灌注压高于 36+/-6mmHg 时会发生收缩，并在线性增加主动壁张力，而无平台期。主动壁张力与灌注压的斜率定义了肌源性反应，3 个月正常或高盐饮食喂养的假手术鼠的肌源性反应相似（2.90+/-0.22 对 3.22+/-0.40 达因 x 厘米-1/毫米 Hg；P 值无显著差异）。在任一种盐饮食 3 天肾单位减少后，肌源性反应无变化（3.39+/-0.61 对 4.04+/-0.47 达因 x 厘米-1/毫米 Hg），但在 3 个月正常和高盐饮食喂养的肾单位减少组的入球小动脉中肌源性反应减弱（2.10+/-0.28 和 1.35+/-0.21 达因 x 厘米-1/毫米 Hg）。结论：在正常灌注压范围内，小鼠肾入球小动脉的肌源性张力呈线性增加。在延长肾单位减少的小鼠模型中，肌源性反应显著受损，尤其是在高盐摄入时。
