Sex and body-type interactions in the regulation of renal sodium transporter levels, urinary excretion, and activity in lean and obese Zucker rats.
Sex and body-type interactions in the regulation of renal sodium transporter levels, urinary excretion, and activity in lean and obese Zucker rats.
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DOI：
10.1016/s1550-8579(06)80219-6
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发表时间：
2006-12-01
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影响因子：
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通讯作者：
Ecelbarger, Carolyn A
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文献类型：
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作者：
Riazi, Shahla;Madala-Halagappa, Veerendra K;Ecelbarger, Carolyn A
背景：女性人类和啮齿类动物相对来说不容易患高血压和肾脏疾病。然而，在胰岛素抵抗和肥胖期间，这种保护作用是否会发生改变尚不清楚。目的：由于肾脏钠重吸收在决定血压中起着核心作用，我们假设瘦雌性大鼠会降低肾脏8种主要钠转运体/通道的表达、活性和尿排泄。方法：在54天的时间里，瘦鼠和肥胖鼠，雄性和雌性Zucker大鼠（每组n = 4-8只）被逐步饲喂高水平的NaCl。在3种不同的饮食水平（0.04%、0.4%和4%）NaCl下测定肾脏钠转运蛋白的尿排泄量。在高盐日粮条件下，将苯甲胺、呋塞米和噻嗪类钠的尿钠反应分别作为上皮钠通道（ENaC）、布美他尼敏感的Na-K-2C1共转运体（NKCC2）和噻嗪类敏感的NaCl共转运体（NCC）活性的体内标志物。结果：雌性大鼠（两种体型）的血浆肾素活性和胰岛素水平低于雄性大鼠。同样，免疫印迹显示，与雄性相比，雌性大鼠的NCC和ENaC的α、β和γ亚基的全肾丰度增加，而3型钠氢交换剂（NHE3）、2型磷酸钠共转运体（NaPi-2）和α -1钠钾腺苷三磷酸酶（na - k - atp酶）的丰度降低。肥胖大鼠的NKCC2、NHE3和γ - enac水平降低，但NaPi-2和NCC水平升高。瘦的雌性大鼠尿液中钠转运体的排泄几乎无法检测到，而肥胖的雌性大鼠尿液中NKCC2和NCC的排泄明显增加，这与噻嗪类和速尿类的利钠反应一致。结论：肥胖雌性大鼠与瘦弱雌性大鼠在肾钠转运蛋白的性别差异模式上相似。然而，肥胖的雌性大鼠在对呋塞米和噻嗪的利钠反应增加以及对包括NCC在内的几种转运蛋白的尿排泄方面更像肥胖的雄性大鼠。我们的研究结果表明，随着肥胖，女性的保护优势在一定程度上丧失了。
BACKGROUND: Female humans and rodents are relatively protected against the development of hypertension and renal disease. Whether this protection is modified during insulin resistance and obesity, however, is not known.OBJECTIVE: Because renal sodium reabsorption has a central role in determining blood pressure, we hypothesized that lean female rats would bave reduced renal expression, activity, and urinary excretion of 8 major sodium transporters/channels.METHODS: Lean and obese, male and female Zucker rats (n = 4-8 per group) were fed progressively higher levels of dietary NaCl over a period of 54 days. Urinary excretion of renal sodium transport proteins was determined for 3 different dietary levels (0.04%, 0.4%, and 4%) of NaCl. With the high-NaCl diet, natriuretic responses to benzamil, furosemide, and thiazide were used as in vivo markers for activity of the epithelial sodium channel (ENaC), the bumetanide-sensitive Na-K-2C1 cotransporter (NKCC2), and the thiazide-sensitive NaCl cotransporter (NCC), respectively.RESULTS: Female rats (of both body types) had lower plasma renin activity and insulin levels than their male counterparts. Likewise, immunoblotting revealed female rats had increased whole kidney abundance of NCC and of the alpha, beta, and gamma subunits of ENaC, as well as decreased abundance of the type 3 sodium hydrogen exchanger (NHE3), type 2 sodium phosphate cotransporter (NaPi-2), and alpha-1 sodium-potassium-adenosine triphosphatase (Na-K-ATPase), compared with males. Obese rats had reduced levels of NKCC2, NHE3, and gamma-ENaC, but higher levels of NaPi-2 and NCC. Urine excretion of sodium transporters in lean female rats was nearly undetectable, whereas obese rats of both sexes excreted markedly more NKCC2 and NCC, which agreed with greater natriuretic responses to thiazide and furosemide.CONCLUSIONS: Obese female rats are similar to lean female rats with regard to the sex-distinct pattern of renal sodium transporters. However, obese female rats are more like obese male rats with regard to increased natriuretic response tofurosemide and thiazide, and to urine excretion of several transporters including NCC. Our results suggest that, with obesity, there is some loss of the protective female advantage.