Mineralocorticoid Receptor Activation and Oxidative Stress

Abstract

The spontaneously hypertensive rat (SHR) has been extensively used in studies of hypertension for decades. More recently, a leptin receptor–deficient SHR (SHR/NDmer-cp; SHR/cp) has been developed as a model for the human metabolic syndrome, characterized by elevated blood pressure, visceral obesity, glucose intolerance, and dyslipidemia. In this issue of Hypertension Nagase et al1 have used the SHR/cp to explore the role of oxidative stress and mineralocorticoid receptor (MR) activation on the renal damage that follows a forced high salt intake. The authors have examined an impressive array of markers of renal structural and functional damage, and show that the antioxidant tempol (partially) and the selective MR antagonist eplerenone (completely) block the renal damage caused by 8% NaCl as drinking solution. In sodium deficiency states aldosterone levels are very high, and MR is very much activated, as evidenced by high levels of sodium retention; in such circumstances, however, no vascular or tubular damage is seen. In contrast, when mineralocorticoid levels are inappropriately high for sodium status—in Conn’s syndrome or experimentally (DOC/salt, aldo/salt rat models)—progressive vascular damage occurs in tissues, some of which are classic aldosterone targets (eg, kidney) and others are not (eg, heart). How MR activation in salt deficiency is homeostatic, whereas in sodium loading it is unambiguously deleterious, is a key question yet to be answered. The data in the Nagase et al article show first that the deleterious effects of salt loading are absolutely dependent on MR activation. Secondly, they …