title: Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats.
abstract: Excessive salt intake is known to preferentially increase blood pressure (BP) and promote kidney damage in young, salt-sensitive hypertensive human and animal models. We have suggested that mineralocorticoid receptor (MR) activation plays a major role in kidney injury in young rats. BP and urinary protein were compared in young (3-wk-old) and adult (10-wk-old) uninephrectomized (UNx) Sprague-Dawley rats fed a high (8.0%)-salt diet for 4 wk. The effects of the MR blocker eplerenone on BP and renal injury were examined in the high-salt diet-fed young UNx rats. Renal expression of renin-angiotensin-aldosterone (RAA) system components and of inflammatory and oxidative stress markers was also measured. The effects of the angiotensin receptor blocker olmesartan with or without low-dose aldosterone infusion, the aldosterone synthase inhibitor FAD286, and the antioxidant tempol were also studied. Excessive salt intake induced greater hypertension and proteinuria in young rats than in adult rats. The kidneys of young salt-loaded rats showed marked histological injury, overexpression of RAA system components, and an increase in inflammatory and oxidative stress markers. These changes were markedly ameliorated by eplerenone treatment. Olmesartan also ameliorated salt-induced renal injury but failed to do so when combined with low-dose aldosterone infusion. FAD286 and tempol also markedly reduced urinary protein. UNx rats exposed to excessive salt at a young age showed severe hypertension and renal injury, likely primarily due to MR activation and secondarily due to angiotensin receptor activation, which may be mediated by inflammation and oxidative stress.
authors.affiliation: Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan. hirookawarazaki@yahoo.co.jp
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kawarazaki
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.forename: Megumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Matsui
authors.forename: Ai
authors.initials: A
authors.lastname: Nagae
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Muraoka
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawarasaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000077545:Eplerenone; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000008:administration & dosage*; D013148:Spironolactone / Q000031:analogs & derivatives; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D018161:Receptors, Mineralocorticoid; D013777:Tetrazoles; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; D000077545:Eplerenone; C437965:olmesartan