Loh Su Yi, Giribabu Nelli, Gholami Khadijeh, Salleh Naguib
Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Arch Biochem Biophys. 2017 Jan 15;614:41-49. doi: 10.1016/j.abb.2016.12.008. Epub 2016 Dec 23.
We hypothesized that higher blood pressure in males than females could be due to testosterone effects on aquaporin (AQP) expression in kidneys.
Orchidectomized adult male Sprague-Dawley (SD) rats received seven days subcutaneous testosterone treatment (125 μg/kg/day or 250 μg/kg/day), with or without flutamide or finasteride. Following completion of treatment, MAP was determined in rats under anaesthesia via carotid artery cannulation. In another cohort of rats, kidneys were removed following sacrifice and AQP-1, 2, 3, 4, 6 and 7 protein and mRNA levels were determined by Western blotting and Real-time PCR respectively. Distribution of AQP subunits' protein in the nephrons were visualized by immunofluorescence.
Testosterone caused MAP, AQP-1, 2, 4, 6 and 7 protein and mRNA levels in kidneys to increase while AQP-3 protein and mRNA levels in kidneys to decrease (p < 0.05). AQP-1 and 7 were found to be distributed in the proximal convoluted tubule (PCT) while AQP-2, 3, 4 and 6 were found to be distributed in the collecting ducts (CD). Effects of testosterone were antagonized by flutamide and finasteride.
Elevated expression of AQP-1, 2, 4, 6 and 7 under testosterone influence in kidneys could lead to increase HO reabsorption which eventually lead to increase in blood pressure.
我们推测男性血压高于女性可能是由于睾酮对肾脏水通道蛋白(AQP)表达的影响。
对成年去势雄性Sprague-Dawley(SD)大鼠进行为期7天的皮下睾酮治疗(125μg/kg/天或250μg/kg/天),同时给予或不给予氟他胺或非那雄胺。治疗结束后,通过颈动脉插管在麻醉状态下测定大鼠的平均动脉压(MAP)。在另一组大鼠中,处死后取出肾脏,分别通过蛋白质印迹法和实时定量PCR测定水通道蛋白-1、2、3、4、6和7的蛋白质和mRNA水平。通过免疫荧光观察水通道蛋白亚基在肾单位中的蛋白质分布。
睾酮使肾脏中的MAP、水通道蛋白-1、2、4、6和7的蛋白质及mRNA水平升高,而水通道蛋白-3的蛋白质及mRNA水平降低(p<0.05)。发现水通道蛋白-1和7分布在近端小管(PCT),而水通道蛋白-2、3、4和6分布在集合管(CD)。氟他胺和非那雄胺可拮抗睾酮的作用。
在睾酮影响下,肾脏中水通道蛋白-1、2、4、6和7的表达升高可导致水重吸收增加,最终导致血压升高。