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Androgens augment proximal tubule transport.

机译:雄激素增加近端小管运输。

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The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 +/- 0.31 vs. 3.31 +/- 0.23 nl x min(-1) x mm(-1), P < 0.01). Luminally perfusing with either enalaprilat (10(-4) M) to inhibit production of angiotensin II or losartan (10(-8) M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blotanalysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.
机译:近端小管包含自主的肾素-血管紧张素系统,该系统独立于循环血管紧张素II调节运输。已知雄激素会增加血管紧张素原的表达,但是雄激素对近端肾小管转运的作用尚不清楚。在这项体内微灌注研究中,我们研究了雄激素对近端小管运输的影响。注射二氢睾丸激素(DHT)的Sprague-Dawley大鼠体内的体积吸收率显着高于注射媒介物的对照大鼠(4.57 +/- 0.31 vs. 3.31 +/- 0.23 nl x min(-1)x mm(-1) ),P <0.01)。用Enalaprilat(10(-4)M)进行光灌注以抑制血管紧张素II的产生或使用losartan(10(-8)M)来阻断血管紧张素受体的产生,这大大降低了DHT治疗大鼠的近端小管体积吸收率程度高于对照组注射的大鼠。使用Northern印迹分析显示,在DHT处理的动物中,血管紧张素原的肾脏表达更高。在两组动物中,通过血管紧张素II的特异性结合确定的血管紧张素受体的表达没有差异。在接受DHT处理的大鼠中,Na / H交换子的刷状边界膜蛋白丰度(在血管紧张素II调节下)也是较高的。接受DHT的大鼠的血压高于对照组,但其肾小球滤过率没有变化。此外,与对照组相比,DHT治疗组的血清血管紧张素II水平较低。这些结果表明,雄激素可能直接上调近端肾小管肾素-血管紧张素系统,增加体积吸收率,从而增加细胞外体积和血压,其次降低血清血管紧张素II水平。

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