Dominik N Mueller

Aldosterone, mineralocorticoid receptors, and vascular inflammation.

Purpose of reviewAldosterone and its mineralocorticoid receptor represent an ancient signaling system. Indeed, the mineralocorticoid receptor is older than its agonist. Both have probably served various functions through the eons and salt preservation may be relatively recent. A large body of evidence suggests that aldosterone conducts signaling in vascular cells and contributes substantially to vascular remodeling and target organ damage. A blood pressure and salt balance-independent effect was first observed in two large heart failure trials. Recent findingsMineralocorticoid receptor blockade has now been shown to reduce proteinuria even in the face of angiotensin converting enzyme inhibition and AT1 receptor blockade. Mineralocorticoid receptor blockade effectively reduces target organ damage in every hypertensive model tested, irrespective of circulating renin and aldosterone levels. Protection is also observed in nonhypertensive diabetic and hyperlipidemic models. Signaling in vascular cells involves primarily the mitogen activated protein kinase pathway with participation of the epidermal growth factor receptor. Novel signaling molecules have been shown to participate in aldosterone-mediated actions including the murine double-minute type 2 protein that participates in antiapoptotic and proliferative effects. Clinically, mutations in the mineralocorticoid receptor have shed additional light on its importance. SummaryA resurgence of interest in aldosterone reflects its importance and clinical relevance for vascular remodeling and target organ damage.

Long-term follow-up of patients with atherosclerotic renal artery disease

Atherosclerotic renal artery stenosis (ARAS) is a predictor of increased morbidity and mortality. However, whether ARAS itself accelerates the arteriosclerotic process or whether ARAS is solely the consequence of atherosclerosis is unclear. We imaged renal arteries of 1561 hypertensive patients undergoing coronary angiography and followed this cohort for 9 years (range, 2.4-15.1 years; median, 31.2 months, interquartile range, 13.4/52.9 months). All patients received aspirin, renin-angiotensin system blockade, statins, and beta blockade as indicated. One hundred seventy-one patients had ARAS >50% diameter stenosis and 126 patients an arteriosclerotic plaque (ARAP) without significant stenosis. Blood pressures were not different in ARAS, ARAP, and non-ARAS patients. After adjustment for cardiovascular risk factors by propensity scores and matched pair analysis, ARAS patients had a lower ejection fraction and more coronary artery disease (CAD) than non-ARAS patients. The same was true for brain natriuretic peptide values, troponin I, and highly sensitive C-reative protein. Over 9 years, more ARAS patients died of any cause (34% vs 23%; P < .05). The prevalence of CAD in ARAP patients was higher than in non-ARAS patients and lower than in ARAS patients. The mortality of the ARAP patients at 9 years was 37%, not different from the ARAS patients. Atherosclerotic renal artery disease appears to be a marker for the severity of atherosclerosis rather than a causative factor for atherosclerosis progression.