Burns K D, Smith I B
Department of Medicine, University of Ottawa, and Ottawa General Hospital, Ont., Canada.
Nephron. 1998;78(1):73-81. doi: 10.1159/000044885.
Dietary potassium (K+) deficiency is associated with blood pressure elevation and impaired urinary sodium excretion. Since angiotensin II is a potent stimulator of tubular sodium transport, we studied the effect of low [K+] on expression of kidney AT1 angiotensin receptors. In rabbits fed a K+-deficient diet for 14 days, plasma [K+] was significantly reduced compared to rabbits fed a standard diet (control: 4.06 +/- 0.12 vs. K+-deficient: 2.66 +/- 0.19 mmol/l; p < 0.001; n = 6-9). By Northern hybridization or RNase protection assays, dietary K+ deficiency caused an increase in mRNA expression for AT1 receptors in kidney cortex (43.5 +/- 12.9% increase vs. control; p < 0.04; n = 8), and in proximal tubule segments in suspension (76.4 +/- 28.8% increase vs. control; p < 0.005; n = 6). K+ deficiency had no effect on AT1 receptor mRNA expression in liver, or on mRNA expression of beta-actin in kidney cortex, proximal tubule suspensions, or liver. To determine if low extracellular [K+] might directly modulate AT1 receptor mRNA expression, primary cultures of rabbit proximal tubule cells were incubated for 1, 3, 6 or 24 h in media with or without 5 mmol/l K+. Incubation of cells in 0 mmol/l K+ caused a 99.2 +/- 32.9% increase in AT1 receptor mRNA expression at 3 h (p < 0.001; n = 14), returning to control levels by 24 h. Incubation of proximal tubule cells in 0 mmol/l K+ also caused a significant increase in basolateral membrane specific binding of [125I]-angiotensin II (p < 0.05; n = 4). These results indicate that dietary K+ deficiency and low extracellular [K+] stimulate expression of kidney AT1 angiotensin II receptors. Increased AT1 receptor mRNA and protein expression in proximal tubule may promote enhanced sodium reabsorption in K+ deficiency.
膳食钾（K+）缺乏与血压升高及尿钠排泄受损有关。由于血管紧张素II是肾小管钠转运的强效刺激物，我们研究了低钾[K+]对肾脏AT1血管紧张素受体表达的影响。给兔子喂食低钾饮食14天，与喂食标准饮食的兔子相比，血浆[K+]显著降低（对照组：4.06±0.12 vs. 低钾组：2.66±0.19 mmol/l；p<0.001；n = 6 - 9）。通过Northern杂交或核糖核酸酶保护分析，膳食钾缺乏导致肾皮质中AT1受体的mRNA表达增加（比对照组增加43.5±12.9%；p<0.04；n = 8），以及悬浮的近端小管节段中增加（比对照组增加76.4±28.8%；p<0.005；n = 6）。钾缺乏对肝脏中AT1受体mRNA表达或肾皮质、近端小管悬浮液或肝脏中β-肌动蛋白的mRNA表达没有影响。为了确定低细胞外[K+]是否可能直接调节AT1受体mRNA表达，将兔近端小管细胞原代培养物在含或不含5 mmol/l K+的培养基中孵育1、3、6或24小时。在0 mmol/l K+中孵育细胞导致3小时时AT1受体mRNA表达增加99.2±32.9%（p<0.001；n = 14），到24小时时恢复到对照水平。在0 mmol/l K+中孵育近端小管细胞也导致[125I]-血管紧张素II的基底外侧膜特异性结合显著增加（p<0.05；n = 4）。这些结果表明，膳食钾缺乏和低细胞外[K+]刺激肾脏AT1血管紧张素II受体的表达。近端小管中AT1受体mRNA和蛋白表达的增加可能促进钾缺乏时钠重吸收增强。
