Turkstra Erika, Braam Branko, Koomans Hein A
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
J Am Soc Nephrol. 2000 May;11(5):847-855. doi: 10.1681/ASN.V115847.
Increases in renal perfusion pressure will induce shear stress-mediated nitric oxide (NO) release, which could oppose autoregulation of renal blood flow (RBF). Although cardiac, cerebral, and mesenteric autoregulation is enhanced during nitric oxide (NO) synthesis inhibition, this has not been reported for renal autoregulation of blood flow. In the present study, the lower limit and efficiency of RBF autoregulation (as assessed by the degree of compensation) were studied before and during NO inhibition in normotensive Sprague Dawley rats (control; n = 9) and in the non-clipped kidney of two-kidney, one-clip Goldblatt hypertensive animals (2K1C; n = 9; 3 wk; 0.25-mm silver clip). In both groups, renal autoregulation curves were obtained before and during infusion of N(G) -nitro-L-arginine (L-NNA) (bolus 1.5 mg/kg intravenously, infusion 10 microg/kg per min intravenously), using a transit-time flow probe around the left renal artery. In control rats, mean arterial pressure (MAP) increased, RBF decreased, and renal vascular resistance (RVR) increased in response to L-NNA infusion. The lower limit of autoregulation in control animals did not significantly change during L-NNA infusion (78 +/- 3 to 70 +/- 2 mmHg). The degree of compensation in these rats slightly increased during L-NNA infusion, however, this was only significant below 90 mmHg. The 2K1C rats had elevated MAP under baseline conditions. L-NNA infusion resulted in a decrease in RBF and an increase in MAP and RVR. During L-NNA infusion, RVR in 2K1C rats greatly exceeded RVR in control rats. A significant decrease was observed in the lower limit of autoregulation from 85 +/- 3 to 72 +/- 5 mmHg (P < 0.05). In the contralateral kidney of 2K1C rats, the degree of compensation was lower than in control rats under baseline conditions. L-NNA infusion resulted in significantly higher degrees of compensation compared to baseline. In conclusion, the contralateral kidney displayed a high NO dependency, as RBF greatly decreased and RVR dramatically increased in response to L-NNA infusion. The contralateral kidney of 2K1C rats exhibited impaired RBF autoregulation, which was improved by NO inhibition, as judged from a decrease in the lower limit of autoregulation and an increase in the degree of compensation. This study indicates that perfusion pressure-dependent NO release can oppose autoregulation in the kidney. However, the enhanced influence of NO on pressure-dependent RBF may facilitate the preservation of renal function in the nonclipped kidney of 2K1C rats.
肾灌注压升高会诱导剪切应力介导的一氧化氮（NO）释放，这可能会对抗肾血流（RBF）的自身调节。尽管在一氧化氮（NO）合成抑制期间心脏、脑和肠系膜的自身调节增强，但肾血流自身调节方面尚未有此报道。在本研究中，研究了正常血压的斯普拉格-道利大鼠（对照组；n = 9）以及两肾一夹戈德布拉特高血压动物（2K1C；n = 9；3周；0.25毫米银夹）未夹闭肾脏在NO抑制前后肾血流自身调节的下限和效率（通过补偿程度评估）。在两组中，使用左肾动脉周围的渡越时间血流探头，在静脉注射N(G)-硝基-L-精氨酸（L-NNA）（静脉推注1.5 mg/kg，静脉输注10 μg/kg每分钟）之前和期间获取肾血流自身调节曲线。在对照大鼠中，静脉注射L-NNA后平均动脉压（MAP）升高、肾血流（RBF）降低以及肾血管阻力（RVR）增加。在静脉注射L-NNA期间，对照动物的自身调节下限没有显著变化（78±3至70±2 mmHg）。这些大鼠的补偿程度在静脉注射L-NNA期间略有增加，然而，仅在90 mmHg以下才具有显著性。2K1C大鼠在基线条件下MAP升高。静脉注射L-NNA导致RBF降低以及MAP和RVR升高。在静脉注射L-NNA期间，2K1C大鼠的RVR大大超过对照大鼠的RVR。自身调节下限从85±3显著降低至72±5 mmHg（P < 0.05）。在2K1C大鼠的对侧肾脏中，基线条件下的补偿程度低于对照大鼠。与基线相比，静脉注射L-NNA导致补偿程度显著更高。总之，对侧肾脏表现出高度的NO依赖性，因为静脉注射L-NNA后RBF大幅降低且RVR显著升高。从自身调节下限降低和补偿程度增加判断，2K1C大鼠的对侧肾脏表现出肾血流自身调节受损，而NO抑制可改善这种情况。本研究表明，灌注压依赖性NO释放可对抗肾脏的自身调节。然而，NO对压力依赖性肾血流的增强影响可能有助于保护2K1C大鼠未夹闭肾脏的肾功能。
