title: Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats.
abstract: 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.
authors.affiliation: Department of Medicine, College of Medicine, Georgetown University, Washington, District of Columbia; jih@georgetown.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Medicine, College of Medicine, Georgetown University, Washington, District of Columbia;
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Medicine, College of Medicine, Georgetown University, Washington, District of Columbia;
authors.forename: Xie
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology and Physiology, College of Medicine, Georgetown University, Washington, District of Columbia; Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida; and.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Speth
authors.affiliation: Department of Medicine, College of Medicine, Georgetown University, Washington, District of Columbia;
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Verbalis
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Stein
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Gina L C
authors.initials: GL
authors.lastname: Yosten
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
authors.affiliation: Department of Medicine, College of Medicine, Georgetown University, Washington, District of Columbia;
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sandberg
mesh_terms: D000302:Adrenal Cortex / Q000254:growth & development* / Q000378:metabolism*; D000375:Aging / Q000652:urine*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001835:Body Weight; D004326:Drinking / Q000187:drug effects; D004435:Eating; D005786:Gene Expression Regulation; D007671:Kidney Concentrating Ability / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D012982:Sodium, Dietary / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary; D001127:Arginine Vasopressin; D000450:Aldosterone
keywords: adrenal cortex; aldosterone; angiotensin type 1 receptor and angiotensin type 2 receptor messenger ribonucleic acid; urine osmolality; urine volume