Mineralocorticoid receptor--Rac1 activation and oxidative stress play major roles in salt-induced hypertension and kidney injury in prepubertal rats.

Objectives: To elucidate the roles that renal mineralocorticoid receptor-Rac1 interactions and oxidative stress play in salt-induced hypertension and renal injury in prepubertal rats.

Methods: Three-week-old male Sprague Dawley rats were uninephrectomized (UNx) and fed a high-salt (8% NaCl) diet for 4 weeks. Five were left untreated, whereas the remaining rats were administered an mineralocorticoid receptor blocker (n = 5), a Rac1 inhibitor (n = 5), a Rho-kinase inhibitor (n = 5), or the superoxide dismutase mimetic tempol (n = 5).

Sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in salt-induced chronic kidney disease.

Hypertension is very prevalent in chronic kidney disease and critical for its prognosis. Sympathoexcitation and oxidative stress have been demonstrated to be involved in chronic kidney disease. We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in the salt-sensitive hypertension model, Dahl salt-sensitive rats.

Rac1 GTPase in rodent kidneys is essential for salt-sensitive hypertension via a mineralocorticoid receptor-dependent pathway.

Hypertension is a leading contributor to cardiovascular mortality worldwide. Despite this, its underlying mechanism(s) and the role of excess salt in cardiorenal dysfunction are unclear. Previously, we have identified cross-talk between mineralocorticoid receptor (MR), a nuclear transcription factor regulated by the steroid aldosterone, and the small GTPase Rac1, which is implicated in proteinuric kidney disease.

Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats.

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.