BACKGROUND Renal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized. METHODS To develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nephrectomy), before and after additional impairment (from the calcium channel blocker amlodipine). We calculated autoregulatory indices for adjacent short segments of increasing length (0.5, 1, 2.5, 5, 10, and 20 seconds) that exhibited a mean BP difference of at least 5 mm Hg. RESULTS Autoregulatory restoration of renal blood flow to baseline after BP changes in conscious rats occurs rapidly, in 5-10 seconds. The response is significantly slower in states of impaired renal autoregulation, enhancing glomerular pressure exposure. However, in rats with severe renal autoregulation impairment (3/4 nephrectomy plus amlodipine), renal blood flow in conscious animals (but not anesthetized animals) was still restored to baseline, but took longer (15-20 seconds). Consequently, the ability to maintain overall renal blood flow stability is not compromised in conscious rats with impaired renal autoregulation. CONCLUSIONS These novel findings show the feasibility of renal autoregulation assessment in conscious animals with spontaneous BP fluctuations and indicate that transient increases in glomerular pressure may play a greater role in the pathogenesis of hypertensive glomerulosclerosis than previously thought. These data also show that unidentified mechanosensitive mechanisms independent of known renal autoregulation mechanisms and voltage-gated calcium channels can maintain overall renal blood flow and GFR stability despite severely impaired renal autoregulation.

中文翻译：

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意识大鼠的血压波动和肾脏血流反应的实时动态。

背景技术尽管有BP波动，但肾脏自律调节可维持稳定的肾功能，并保护肾小球毛细血管免受高血压损伤。然而，意识动物的肾脏自动调节的实时动态尚未被表征。方法为了开发评估肾自动调节的新颖分析方法，我们记录了清醒大鼠的并发BP和肾血流量，比较了在其他损害（来自钙）和完整（受损）肾脏自调节（来自3/4肾切除术）的动物的情况。通道阻滞剂氨氯地平）。我们计算了长度增加（0.5、1、2.5、5、10和20秒）的相邻短段的自动调节指数，这些短段显示出至少5 mm Hg的平均BP差。结果在有意识的大鼠中BP改变后，肾脏血流自动调节恢复到基线，在5-10秒内迅速发生。在肾自动调节受损的状态下，反应明显减慢，从而增加肾小球压力暴露。但是，在患有严重肾脏自身调节功能障碍（3/4肾切除术加氨氯地平）的大鼠中，清醒动物（而非麻醉动物）的肾血流仍恢复到基线水平，但需要更长的时间（15-20秒）。因此，在肾自律调节受损的清醒大鼠中，维持总体肾血流稳定性的能力不会受到损害。结论这些新发现表明，在具有自发性BP波动的清醒动物中进行肾脏自体调节评估的可行性，并表明肾小球压力的短暂升高可能在高血压性肾小球硬化的发病机理中发挥了更大的作用。这些数据还表明，尽管严重损害了肾脏的自我调节能力，但与已知的肾脏自动调节机制和电压门控钙通道无关的不确定的机械敏感机制仍可以维持总体肾血流量和GFR稳定性。