Kaufmann M A, Pargger H, Castelli I, Steiner L A, Drop L J
Henry K. Beecher Laboratory, Massachusetts General Hospital, Boston 02114, USA.
J Trauma. 1996 Jan;40(1):110-5. doi: 10.1097/00005373-199601000-00020.
The aim of this study was to examine the influence of norepinephrine (NE) on renal vascular responses to high (1.88 mmol/L) and low (0.56 mmol/L) perfusate-ionized calcium ([Ca2+]) in the isolated perfused kidney of the rat. High and low [Ca2+] encompassed the clinical concentration range in this multiexperiment, randomized trial.
Rats (n = 25), ranging in age from 3 to 4 months, were anesthetized and the ureter and renal artery were cannulated. The right kidney was perfused with oxygenated, warmed albumin (67 g/L) containing Krebs-Henseleit buffer and placed in a thermostated chamber without interruption of flow. In protocol A (n = 7), steady-state high [Ca2+] (1.88 mmol/L) and low [Ca2+] (0.56 mmol/L) were instituted in randomized order in each experiment under basal conditions. In protocol B (n = 9), the same interventions were instituted during constant rate NE infusion. Changes in renal flow were measured at constant perfusion pressure (110 mm Hg), and renal vascular resistance (RVR) was calculated. Renal function was assessed by clearance of [14C]inulin and by fractional excretion of sodium. With NE-induced preconstriction, the increase in RVR observed during high [Ca2+] was +17.8 +/- 1.8% of control, and the decrease in RVR observed during low [Ca2+] was -35.9 +/- 8.2% of control. Both values were greater by a factor of 2 than corresponding results obtained under basal conditions (7 +/- 2.1% vs. -13.5 +/- 4.1% of control, respectively, p < 0.05). Whereas the decrease in glomerular filtration rate with high [Ca2+] was not significantly influenced by NE pretreatment (-9 +/- 1.8% of control with high [Ca2+] in combination with NE vs. 4.1 +/- 0.7% of control under basal conditions), the increase in glomerular filtration rate with low [Ca2+] was significantly greater in the presence of NE (12 +/- 0.7 vs. 102 +/- 8.5% of control, p < 0.01).
Whereas under basal conditions renal vascular effects of high and low [Ca2+] (varied within the clinical concentration range) are small, the changes recorded with the same interventions after NE pretreatment are increased by a factor of > 2. Hypercalcemia-induced renovascular constriction and decreased function are unfavorable, especially in patients who are at risk for renal dysfunction from other causes.
本研究旨在探讨去甲肾上腺素（NE）对大鼠离体灌流肾脏中高（1.88 mmol/L）、低（0.56 mmol/L）灌注液离子钙（[Ca2+]）时肾血管反应的影响。在这项多实验随机试验中，高、低[Ca2+]涵盖了临床浓度范围。
选用25只年龄在3至4个月的大鼠，进行麻醉并插管至输尿管和肾动脉。右肾用含Krebs-Henseleit缓冲液的氧合、加温白蛋白（67 g/L）进行灌注，并置于恒温箱中，灌注过程不间断。在方案A（n = 7）中，在基础条件下，每次实验以随机顺序设置稳态高[Ca2+]（1.88 mmol/L）和低[Ca2+]（0.56 mmol/L）。在方案B（n = 9）中，在持续输注NE期间进行相同的干预。在恒定灌注压力（110 mmHg）下测量肾血流量，并计算肾血管阻力（RVR）。通过[14C]菊粉清除率和钠排泄分数评估肾功能。在NE诱导的预收缩情况下，高[Ca2+]期间观察到的RVR增加为对照值的 +17.8 +/- 1.8%，低[Ca2+]期间观察到的RVR降低为对照值的 -35.9 +/- 8.2%。这两个值均比基础条件下获得的相应结果大2倍（分别为对照值的7 +/- 2.1% 与 -13.5 +/- 4.1%，p < 0.05）。虽然高[Ca2+]时肾小球滤过率的降低不受NE预处理的显著影响（高[Ca2+]联合NE时为对照值的 -9 +/- 1.8%，而基础条件下为4.1 +/- 0.7%），但在NE存在的情况下，低[Ca2+]时肾小球滤过率的增加显著更大（分别为对照值的12 +/- 0.7% 与102 +/- 8.5%，p < 0.01）。
在基础条件下，高、低[Ca2+]（在临床浓度范围内变化）对肾血管的影响较小，但NE预处理后相同干预措施记录到的变化增加了2倍以上。高钙血症引起的肾血管收缩和功能降低是不利的，尤其是对于因其他原因有肾功能障碍风险的患者。
