Broman Lars Mikael, Carlström Mattias, Källskog Örjan, Wolgast Mats
ECMO Centre Karolinska, Department of Pediatric Perioperative Medicine and Intensive Care, Karolinska University Hospital, 171 76, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden.
Pflugers Arch. 2017 Jun;469(5-6):669-680. doi: 10.1007/s00424-017-1967-1. Epub 2017 Mar 17.
Hypothermia-induced reduction of metabolic rate is accompanied by depression of both glomerular perfusion and filtration. The present study investigated whether these changes are linked to changes in renal autoregulation and nitric oxide (NO) signalling. During hypothermia, renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced and urine production was increased, and this was linked with reduced plasma cGMP levels and increased renal vascular resistance. Although stimulation of NO production decreased vascular resistance, blood pressure and urine flow, intravenous infusion of the NO precursor L-arginine or the NO donor sodium nitroprusside did not alter RBF or GFR. In contrast, inhibition of NO synthesis by N-nitro-L-arginine led to a further decline in both parameters. Functional renal autoregulation was apparent at both temperatures. Below the autoregulatory range, RBF in both cases increased in proportion to the perfusion ±pressure, although, the slope of the first ascending limb of the pressure-flow relationship was lower during hypothermia. The main difference was rather that the curves obtained during hypothermia levelled off already at a RBF of 3.9 ± 0.3 mL/min then remained stable throughout the autoregulatory pressure range, compared to 7.6 ± 0.3 mL/min during normothermia. This was found to be due to a threefold increase in, primarily, the afferent arteriolar resistance from 2.6 to 7.5 mmHg min mL. Infusion of sodium nitroprusside did not significantly affect RBF during hypothermia, although a small increase at pressures below the autoregulatory range was observed. In conclusion, cold-induced rise in renal vascular resistance results from afferent arteriolar vasoconstriction by the autoregulatory mechanism, setting RBF and GFR in proportion to the metabolic rate, which cannot be explained by reduced NO production alone.
体温过低引起的代谢率降低伴随着肾小球灌注和滤过的抑制。本研究调查了这些变化是否与肾自动调节和一氧化氮（NO）信号传导的变化有关。在体温过低期间，肾血流量（RBF）和肾小球滤过率（GFR）降低，尿量增加，这与血浆环鸟苷酸（cGMP）水平降低和肾血管阻力增加有关。尽管刺激NO生成可降低血管阻力、血压和尿流，但静脉输注NO前体L-精氨酸或NO供体硝普钠并不会改变RBF或GFR。相反，N-硝基-L-精氨酸抑制NO合成会导致这两个参数进一步下降。在两个温度下均存在功能性肾自动调节。在自动调节范围以下，两种情况下的RBF均与灌注±压力成比例增加，尽管在体温过低期间压力-流量关系的第一个上升支的斜率较低。主要区别在于，与正常体温下的7.6±0.3 mL/min相比，体温过低期间获得的曲线在RBF为3.9±0.3 mL/min时就趋于平稳，然后在整个自动调节压力范围内保持稳定。发现这是由于主要是入球小动脉阻力从2.6 mmHg·min/mL增加到7.5 mmHg·min/mL，增加了三倍。输注硝普钠在体温过低期间对RBF没有显著影响，尽管在低于自动调节范围的压力下观察到有小幅增加。总之，寒冷诱导的肾血管阻力增加是由自动调节机制引起的入球小动脉血管收缩所致，使RBF和GFR与代谢率成比例，这不能仅用NO生成减少来解释。
