The role of aldosterone in resistant hypertension: Implications for pathogenesis and therapy

Abstract

Resistant hypertension constitutes an increasingly common medical disorder. Although the exact incidence is not precisely known, estimates derived from recent outcome studies emphasize that resistant hypertension is much more common than previously thought. A major advance in our understanding of its pathogenesis and management is the recent recognition of the importance of aldosterone excess or autonomy as an important mechanism for drug resistance in hypertension. Recent studies of the effects of aldosterone on vascular smooth muscle have delineated several extra-renal mechanisms whereby aldosterone produces hypertension primarily by its direct vasoconstrictor effects and by altering vascular compliance. Consequently, aldosterone blockade constitutes an effective intervention for treating resistant hypertension.

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

“…Mineralocorticoid blockade has been demonstrated to be effective in reducing total mortality as well as hospitalization for heart failure in patients with systolic left ventricular dysfunction due to chronic heart failure and in patients with congestive heart failure following acute myocardial infarction [170,171]. Sodium retention and volume expansion mediated in part by aldosterone excess are prominent features in low-renin hypertension and the use of these agents in hypertensive diabetic patients, as well as those with resistant hypertension, are emerging [172]. In a recent study, eplerenone was demonstrated to be more effective than losartan in reducing BP in patients with low-renin hypertension typical of T2DM [173].…”

“…The mechanism of action of aldosterone antagonists have been well defined over the years in regards to the myocardium, congestive heart failure and hypertension [168][169][170][171][172], and recently there has been increased interest regarding its effect in the CMS [174,175]. Our laboratory has recently found evidence to support a positive role for the attenuation of NAD(P)H oxidase production of oxidative stress in the myocardium and cardiac remodeling utilizing mineralocorticoid receptor blockade with low-dose spironolactone in the Ren2 model of hypertension, oxidative stress, and IR [176].…”

Clinical approach in treatment of resistant hypertension

“…The prevalence of PA tends to increase with increasingly severe hypertension 24. PA may be associated with both obesity and OSA 1…”

“…Aldosterone has been demonstrated to exert a number of influences leading to increased systemic vascular resistance including an association with endothelial dysfunction, vascular remodeling through collagen deposition, vascular damage, impairment of the baroreflex leading to loss of compensation for elevated blood pressure, and hypervolemia 2,24,25. Aldosterone may promote both renal and cardiovascular injury by mechanisms other than blood pressure elevation 24.…”

“…Aldosterone may promote both renal and cardiovascular injury by mechanisms other than blood pressure elevation 24. Aldosterone excess, in the absence of diagnosed primary aldosteronism, may contribute to resistant hypertension as evidenced by the benefit of aldosterone antagonists in patients both with and without PA as well as the demonstration of biochemical markers of aldosterone excess in patients with RH 8.…”