Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Nephrology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; and.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Am J Physiol Renal Physiol. 2014 May 15;306(10):F1190-7. doi: 10.1152/ajprenal.00073.2014. Epub 2014 Apr 2.
Metabolic and functional abnormalities in the kidney precede or coincide with the initiation of overt hypertension in the Dahl salt-sensitive (SS) rat. However, renal histological injury in SS rats is mild before the development of overt hypertension. We performed electron microscopy analysis in 7-wk-old SS rats and salt-insensitive consomic SS.13(BN) rats and Sprague-Dawley (SD) rats fed a 4% NaCl diet for 7 days. Long mitochondria (>2 μm) accounted for a significantly smaller fraction of mitochondria in medullary thick ascending limbs in SS rats (4% ± 1%) than in SS.13(BN) rats (8% ± 1%, P < 0.05 vs. SS rats) and SD rats (9% ± 1%, P < 0.01 vs. SS rats), consistent with previous findings of mitochondrial functional insufficiency in the medulla of SS rats. Long mitochondria in proximal tubules, however, were more abundant in SS rats than in SS.13(BN) and SD rats. The width of the endoplasmic reticulum, an index of endoplasmic reticulum stress, was significantly greater in medullary thick ascending limbs of SS rats (107 ± 1 nm) than in SS.13(BN) rats (95 ± 2 nm, P < 0.001 vs. SS rats) and SD rats (74 ± 3 nm, P < 0.01 vs. SS or SS.13(BN) rats). The tubules examined were indistinguishable between rat strains under light microscopy. These data indicate that ultrastructural abnormalities occur in the medullary thick ascending limbs of SS rats before the development of histological injury in renal tubules, providing a potential structural basis contributing to the subsequent development of overt hypertension.
在达尔盐敏感（SS）大鼠中，肾脏的代谢和功能异常先于或与明显高血压的发生同时发生。然而，在明显高血压发生之前，SS 大鼠的肾脏组织学损伤较轻。我们对 7 周龄 SS 大鼠和盐不敏感同基因 SS.13(BN)大鼠以及 Sprague-Dawley（SD）大鼠进行了电子显微镜分析，这些大鼠均喂食 4%NaCl 饮食 7 天。长线粒体（>2μm）在 SS 大鼠的髓质升支粗段中占比明显小于 SS.13(BN)大鼠（8%±1%，P<0.05 与 SS 大鼠相比）和 SD 大鼠（9%±1%，P<0.01 与 SS 大鼠相比），这与 SS 大鼠髓质线粒体功能不足的先前发现一致。然而，近端小管中的长线粒体在 SS 大鼠中更为丰富。内质网的宽度，即内质网应激的指标，在 SS 大鼠的髓质升支粗段中明显大于 SS.13(BN)大鼠（107±1nm，P<0.001 与 SS 大鼠相比）和 SD 大鼠（74±3nm，P<0.01 与 SS 或 SS.13(BN)大鼠相比）。在光镜下，不同大鼠品系的肾小管没有区别。这些数据表明，在肾小管发生组织学损伤之前，SS 大鼠的髓质升支粗段就已经出现了超微结构异常，这为随后发生明显高血压提供了潜在的结构基础。
