Forster H G, ter Wee P M, Takenaka T, Hohman T C, Epstein M
Nephrology Section, Department of Veterans Affairs Medical Center, Miami, Florida 33125.
Proc Soc Exp Biol Med. 1994 Sep;206(4):365-74. doi: 10.3181/00379727-206-43773.
Previous studies from our laboratory have demonstrated impaired afferent arteriolar responsiveness to pressure in rats 4-6 weeks after the induction of diabetes mellitus. Although the responsible mechanisms mediating this renal autoregulatory defect have not been fully defined, increased polyol metabolism has been implicated as a possible factor involved in the pathogenesis of diabetic complications. We therefore investigated the possible role of this metabolic disturbance in renal autoregulation using the galactose-fed rat, a model characterized by increased polyol pathway activity independent of hyperglycemia or insulin deficiency. Hydronephrosis was induced to permit direct visualization of renal microvessels. Pressure-induced vasoconstriction of afferent arterioles was assessed by quantitating vessel diameter following stepwise increments of renal perfusion pressure (RAP; from 80 to 180 mm Hg) in the hydronephrotic kidneys from control rats and rats fed a 50% galactose diet for 2 or 4 weeks. Vessel diameters were measured from video images by computer-assisted image processing. Control rats exhibited progressive afferent arteriolar vasoconstriction when RAP was increased from 80 to 180 mm Hg (-17.3% +/- 1.0%; P < 0.001). In contrast, myogenic responses to increases in pressure were absent in the afferent arterioles of rats fed a 50% galactose diet for either 2 (-4.1% +/- 1.9%; not significant) or 4 weeks (-2.9 +/- 3.4%; not significant). Our demonstration that the impairment of afferent arteriolar responsiveness to increasing RAP in the normoglycemic galactose-fed rat was identical to that observed in the STZ-diabetic rat suggests that increased polyol accumulation may contribute to the impairment of renal autoregulation in the diabetic rat.
我们实验室之前的研究表明，在诱导糖尿病4 - 6周后的大鼠中，传入小动脉对压力的反应性受损。尽管介导这种肾脏自身调节缺陷的相关机制尚未完全明确，但多元醇代谢增加被认为是糖尿病并发症发病机制中可能涉及的一个因素。因此，我们使用半乳糖喂养的大鼠来研究这种代谢紊乱在肾脏自身调节中的可能作用，该模型的特征是多元醇途径活性增加，且与高血糖或胰岛素缺乏无关。诱导肾积水以便直接观察肾微血管。通过在对照大鼠和喂食50%半乳糖饮食2周或4周的大鼠的肾积水肾脏中，逐步增加肾灌注压（RAP；从80至180 mmHg）后定量血管直径，来评估压力诱导的传入小动脉血管收缩。通过计算机辅助图像处理从视频图像中测量血管直径。当RAP从80 mmHg增加到180 mmHg时，对照大鼠表现出渐进性的传入小动脉血管收缩（-17.3% +/- 1.0%；P < 0.001）。相比之下，喂食50%半乳糖饮食2周（-4.1% +/- 1.9%；无显著性差异）或4周（-2.9 +/- 3.4%；无显著性差异）的大鼠的传入小动脉对压力增加没有肌源性反应。我们证明，在血糖正常的半乳糖喂养大鼠中，传入小动脉对RAP增加的反应性受损与在链脲佐菌素诱导的糖尿病大鼠中观察到的情况相同，这表明多元醇积累增加可能导致糖尿病大鼠肾脏自身调节受损。
