Burke T J, Cronin R E, Duchin K L, Peterson L N, Schrier R W
Am J Physiol. 1980 Apr;238(4):F305-14. doi: 10.1152/ajprenal.1980.238.4.F305.
The pathogenetic factors involved in norepinephrine- (NE) induced reversible acute renal failure (ARF) were examined in untreated (U) and mannitol-treated (M) animals. At 3 and 24 h after NE infusion renal blood flow (RBF) was significantly higher in M compared to U animals (174 vs. 138 and 191 vs. 148 ml/min, respectively, both P less than 0.05). At 3 h, glomerular filtration rate (GFR) was higher in M animals (8 vs. 4 ml/min, P less than 0.01), while at 24 h protection was even greater (18 vs. 3 ml/min, P less than 0.01). In U animals proximal tubule pressure (Pt) was lower at 1 h than before NE (13 vs. 23 mmHg, P less than 0.01); from 1 to 3 h Pt increased to elevated levels in parallel with restoration of RBF (r = 0.62, P less than 0.01). At 3 h in U animals stop-flow pressure (SFP), as an index of glomerular capillary pressure, was below normal (35 vs. 44 mmHg, P less than 0.05) yet Pt was increased (35 vs. 23 mmHg, P less than 0.05). Thus little transglomerular pressure gradient was present for ultrafiltration. Further evidence of tubular obstruction was obtained by microperfusion at 6 nl/min, which increased Pt from 30 to 45 mmHg (P less than 0.001), a finding not present in unobstructed tubules. Delayed excretion (approximately 20 min) of microinjected [3H]inulin also was compatible with renal ischemia and tubule obstruction. Microinjection studies provided no evidence for backleak of tubular fluid. At 1 h, Pt was higher in M vs. U animals (31 vs. 13 mmHg, P less than 0.05). In M animals at 3 h SFP was normal (50 vs. 44 mmHg) and Pt was below SFP (32 vs. 50 mmHg, P less than 0.01), thus preserving a substantial transglomerular pressure gradient for ultrafiltration. In summary, reduced GFR in U animals is characterized by a combination of reduced glomerular capillary pressure and tubule obstruction. In contrast, animals receiving mannitol were protected against ARF through maintenance of glomerular capillary pressure and prevention of tubular obstruction, perhaps by increasing Pt within the first hour of the NE insult.
在未治疗（U）和甘露醇治疗（M）的动物中，研究了去甲肾上腺素（NE）诱导的可逆性急性肾衰竭（ARF）的发病机制。在输注NE后3小时和24小时，M组动物的肾血流量（RBF）显著高于U组动物（分别为174 vs. 138和191 vs. 148 ml/分钟，P均小于0.05）。在3小时时，M组动物的肾小球滤过率（GFR）较高（8 vs. 4 ml/分钟，P小于0.01），而在24小时时保护作用更强（18 vs. 3 ml/分钟，P小于0.01）。在U组动物中，近端小管压力（Pt）在1小时时低于输注NE前（13 vs. 23 mmHg，P小于0.01）；从1小时到3小时，Pt随着RBF的恢复而升高至升高水平（r = 0.62，P小于0.01）。在U组动物中，3小时时作为肾小球毛细血管压力指标的停流压力（SFP）低于正常水平（35 vs. 44 mmHg，P小于0.05），但Pt升高（35 vs. 23 mmHg，P小于0.05）。因此，超滤的跨肾小球压力梯度很小。通过以6 nl/分钟的速度进行微灌注获得了肾小管阻塞的进一步证据，这使Pt从30 mmHg增加到45 mmHg（P小于0.001），这一发现不存在于未阻塞的肾小管中。微量注射的[3H]菊粉排泄延迟（约20分钟）也与肾缺血和肾小管阻塞相符。微量注射研究未提供肾小管液回漏的证据。在1小时时，M组动物的Pt高于U组动物（31 vs. 13 mmHg，P小于0.05）。在M组动物中，3小时时SFP正常（五十vs. 44 mmHg），Pt低于SFP（32 vs. 50 mmHg，P小于0.01），因此保留了较大的超滤跨肾小球压力梯度。总之，U组动物中GFR降低的特征是肾小球毛细血管压力降低和肾小管阻塞共同作用。相比之下，接受甘露醇治疗的动物通过维持肾小球毛细血管压力和预防肾小管阻塞而免受ARF的影响，这可能是通过在NE损伤的第一小时内增加Pt来实现的。
