Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats

作者：Ji Hong^*; Zheng Wei; Wu Xie; Speth Robert C; Verbalis Joseph G; Stein Lauren M; Yosten Gina L C; Samson Willis K; Sandberg Kathryn

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2016, 310(6): R513-R521.

DOI：10.1152/ajpregu.00131.2015

• angiotensin type 1 receptor and angiotensin type 2 receptor messenger ribonucleic acid
• urine volume
• urine osmolality
• aldosterone
• adrenal cortex

To investigate age-associated impairments in fluid homeostasis, 4-mo (young) and 32-mo (old) Fischer 344/BN male rats were studied before and after a dietary sodium load. Transferring young rats from a low-sodium (LS) to a high-sodium (HS) diet increased water intake and urine volume by 1.9- and 3.0-fold, respectively, while urine osmolality and plasma aldosterone decreased by 33 and 98%. Concomitantly, adrenocortical angiotensin type 1 receptor (AT(1)R) density decreased by 35%, and AT(1b)R mRNA decreased by 39%; no changes were observed in AT(1a)R mRNA. In contrast, the increase in water intake (1.4-fold) was lower in the old rats, and there was no effect of the HS diet on urine volume or urine osmolality. AT(1)R densities were 29% less in the old rats before transferring to the HS diet, and AT(1)R densities were not reduced as rapidly in response to a HS diet compared with the young animals. After 6 days on the HS diet, plasma potassium was lowered by 26% in the old rats, whereas no change was detected in the young rats. Furthermore, while plasma aldosterone was substantially decreased after 2 days on the HS diet in both young and old rats, plasma aldosterone was significantly lower in the old compared with the young animals after 2 wk on the LS diet. These findings suggest that aging attenuates the responsiveness of the adrenocortical AT(1)R to a sodium load through impaired regulation of AT(1b)R mRNA, and that this dysregulation contributes to the defects in water and electrolyte homeostasis observed in aging.

• 出版日期2016-3-15
• 单位东南大学