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首页> 外文期刊>Journal of Cellular Physiology >Compromised regulation of the collecting duct ENaC activity in mice lacking AT 1a 1a receptor
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Compromised regulation of the collecting duct ENaC activity in mice lacking AT 1a 1a receptor

机译：妥协的规定收集管钠活动1 a受体在小鼠缺乏1

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ENaC‐mediated sodium reabsorption in the collecting duct (CD) is a critical determinant of urinary sodium excretion. Existing evidence suggest direct stimulatory actions of Angiotensin II (Ang II) on ENaC in the CD, independently of the aldosterone‐mineralocorticoid receptor (MR) signaling. Deletion of the major renal AT 1 receptor isoform, AT 1a R, decreases blood pressure and reduces ENaC abundance despite elevated aldosterone levels. The mechanism of this insufficient compensation is not known. Here, we used patch clamp electrophysiology in freshly isolated split‐opened CDs to investigate how AT 1a R dysfunction compromises functional ENaC activity and its regulation by dietary salt intake. Ang II had no effect on ENaC activity in CDs from AT 1a R ?/? mice suggesting no complementary contribution of AT 2 receptors. We next found that AT 1a R deficient mice had lower ENaC activity when fed with low (0.01% Na + ) and regular (0.32% Na + ) but not with high (～2% Na + ) salt diet, when compared to the respective values obtained in Wild type (WT) animals. Inhibition of AT 1 R with losartan in wild‐type animals reproduces the effects of genetic ablation of AT 1a R on ENaC activity arguing against contribution of developmental factors. Interestingly, manipulation with aldosterone‐MR signaling via deoxycosterone acetate (DOCA) and spironolactone had much reduced influence on ENaC activity upon AT 1a R deletion. Consistently, AT 1a R ?/? mice have a markedly diminished MR abundance in cytosol. Overall, we conclude that AT 1a R deficiency elicits a complex inhibitory effect on ENaC activity by attenuating ENaC P o and precluding adequate compensation via aldosterone cascade due to decreased MR availability.
机译：钠介导钠的重吸收收集管(CD)是一个关键的决定因素尿钠排泄。表明血管紧张素的直接刺激行动二世(Angⅱ)钠在CD上,独立的醛固酮检测盐皮质激素受体(MR)信号。1 R受体同种型,减少血液压力和减少钠丰富尽管醛固酮水平升高。这不足补偿是未知的。在这里,我们使用膜片钳电生理新孤立分割量打开cd进行调查1 R功能障碍妥协功能如何博活动及其监管,食用盐的摄入量。cd从1 R / ?补充2受体的贡献。下发现1 R缺乏小鼠低博活动当美联储较低(Na + & 0.01%)和常规(Na + 0.32%)但不高(~ 2%Na +)盐饮食,相比各自的在野生型(WT)动物获得的值。抑制1 R和洛沙坦在野生型动物繁殖遗传的影响消融在1 R ENaC活动的争论对发展的贡献因素。有趣的是,操纵与醛固酮所致通过醋酸deoxycosterone (DOCA)和信号螺内酯对博大幅减少的影响活动在1 R删除。1 R ? / ?在胞质丰富。1 R缺乏抒发复杂的抑制影响钠活动衰减ENaC P o通过,从而排除适当补偿由于减少醛固酮级联可用性。

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