Kawarazaki H, Ando K, Fujita M, Matsui H, Nagae A, Muraoka K, Kawarasaki C, Fujita T. Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats. Am J Physiol Renal Physiol 300: F1402-F1409, 2011. First published April 6, 2011 doi:10.1152/ajprenal.00691.2010.-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-angiotensinaldosterone (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. salt sensitivity; aldosterone; oxidative stress; renin-angiotensin OBSERVATIONAL STUDIES HAVE suggested that increased blood pressure (BP) in childhood correlates with increased BP in adulthood (36). Hypertension is closely related to kidney dysfunction, which can cause increased BP. Therefore, both BP control and maintenance of kidney health at a young age may be critical for BP management later in life.Salt consumption among very young children has increased in developed countries at a faster rate than in developing countries (9,28,33). It is believed that high salt (HS) intake during prepuberty contributes to high BP later in life (1, 23). In addition, increased BP resulting from excessive salt consumption has been shown to be enhanced in the young in several animal models of salt-sensitive (SS) hypertension (35). We previously demonstrated that in Dahl SS rats, an SS hypertension model, HS intake at a young age accelerates the development of kidney injury and hypertension (12). Interestingly, salt restriction during infant weaning has been reported to lo...