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Title: Aldosterone Antagonists Prevent RAAS Escape and May Help Prevent Target Organ Damage

URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
Retrieve&db=PubMed&dopt=Abstract&list_uids=12948434

Curr Hypertens Rep 2003;5:5:408-417. "RAAS Escape: A Real Clinical Entity that May Be Important in the Progression of Cardiovascular and Renal Disease"
09/17/2003 10:47:00 AM
By Emma Hitt, PhD

Aldosterone receptor antagonists can inhibit renin-angiotensin-aldosterone system (RAAS) escape mechanisms that can occur during therapeutic RAAS blockade and may be useful in preventing target-organ injury, according to a review article on the subject. In their report, Jay Lakkis, MD, with the Division of Nephrology at the University of Maryland School of Medicine, Baltimore, United States, and colleagues discussed aldosterone receptor antagonists and implications for their use. Aberrations in the RAAS have been implicated in congestive heart failure, elevated arterial blood pressure, kidney disease, and other disease states, while agents that target the RAAS, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to be protective in multiple ways. However, in patients taking these agents, RAAS escape involving aldosterone synthesis may allow heart and kidney disease progression. According to the researchers, aldosterone may help mediate several pathogenic states, including hypertension, vascular smooth muscle hypertrophy, endothelial dysfunction, structural renal injury, proteinuria, and myocardial fibrosis. "Some patients on long-term ACE inhibitor or ARB therapy fail to show any suppression in serum aldosterone levels, while others have an initial phase of suppression but later develop 'escape,'" Dr. Lakkis and colleagues note. Aldosterone receptor antagonists appear to antagonize the effects of RAAS escape in experimental animal models. Furthermore, clinical trials have shown that aldosterone antagonists improve survival and left ventricular mass index in patients with congestive heart failure. They have also been found to reduce proteinuria and left ventricular mass index in patients with type 2 diabetes and early nephropathy and who developed aldosterone synthesis escape. Two aldosterone antagonists, spironolactone and eplerenone, have been studied. Both are competitive mineralocorticoid receptor antagonists. Spironolactone is also an oestrogen and progesterone receptor agonist, which causes related side effects. In contrast, eplerenone has little agonist activity for these receptors. Clinical trials suggest that both agents can cause severe hyperkalemia, however. The researchers conclude that selective aldosterone receptor antagonism "provides an incremental opportunity to protect the kidney and the cardiovascular system, in addition to ACE inhibitor or ARB therapy, by inhibiting the effects of aldosterone that persist despite therapy with these drugs." "The long-term safety of this form of combination therapy needs to be tested in long-term clinical trials," they add.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
Retrieve&db=PubMed&dopt=Abstract&list_uids=12948434

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