Faculty Articles

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



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American Journal of Physiology - Regulatory, Integrative and Comparative Physiology





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American Physiological Society

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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 (AT1R) density decreased by 35%, and AT1bR mRNA decreased by 39%; no changes were observed in AT1aR 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. AT1R densities were 29% less in the old rats before transferring to the HS diet, and AT1R 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 AT1R to a sodium load through impaired regulation of AT1bR mRNA, and that this dysregulation contributes to the defects in water and electrolyte homeostasis observed in aging.


Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences


Adrenal Cortex, Aging, Aldosterone, Animals, Arginine Vasopressin, Body Weight, Drinking, Eating, Gene Expression Regulation, Kidney Concentrating Ability, Male, Osmolar Concentration, RNA, Messenger, Rats, Rats, Inbred F344, Receptor, Angiotensin, Type 1, Sodium, Dietary

MeSH Subject Heading

Adrenal Cortex / growth & development*, Adrenal Cortex / metabolism*, Aging / urine*, Aldosterone / blood, Animals, Arginine Vasopressin / blood, Body Weight, Drinking / drug effects, Eating, Gene Expression Regulation, Kidney Concentrating Ability / physiology*, Male, Osmolar Concentration, RNA, Messenger / biosynthesis, RNA, Messenger / genetics, Rats, Rats, Inbred F344, Receptor, Angiotensin, Type 1 / biosynthesis*, Receptor, Angiotensin, Type 1 / genetics, Sodium, Dietary / pharmacology


© 2016 the American Physiological Society

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