Key result
Endothelin receptor antagonists abrogate the progression of renal failure and prevent cardiac structural alterations in animal models, highlighting their potential for human therapy.
Why the study?
Do endothelin receptor antagonists prevent the progression of renal failure and cardiovascular remodeling in renal disease?
Do endothelin receptor antagonists prevent the progression of renal failure and cardiovascular remodeling in renal disease?
Preclinical evidence suggests that endothelin receptor antagonists may be a promising therapeutic tool to halt the progression of chronic renal failure and associated cardiovascular remodeling, though prospective human trials are needed.
Preclinical renal-cardiac benefits in animals leave open translation to human CKD; prospective trials required before practice change.
The pathogenetic mechanisms leading to progression of renal failure are only partly understood. Several studies in immune- and non-immune-mediated models of renal damage have recently implicated the endothelin (ET) system as a major player in these processes. In animal models, ET receptor antagonists have been shown to be highly effective in abrogating the progression of renal failure. Furthermore, cardiac structural alterations seen in hypertension and/or renal insufficiency, e.g. left ventricular hypertrophy, thickening of intramyocardial arterioles, and the increase in non-vascular interstitial tissue, are largely prevented by ET receptor antagonists. In this context it is of interest that these beneficial renal and cardiac effects are, at least in most studies, independent of systemic blood pressure. In addition to the specific pharmacological blockade of the renin-angiotensin system [ACE inhibitors, angiotensin II receptor (AT1) antagonists], blockade of ET receptors or ET converting enzyme (ECE) may be a new tool to interfere with progression of renal failure and cardiovascular remodeling in humans.
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Orth et al. (2001) conducted a review in Renal failure and cardiovascular remodeling. Endothelin receptor antagonists was evaluated. Endothelin receptor antagonists abrogate the progression of renal failure and prevent cardiac structural alterations in animal models, highlighting their potential for human therapy.
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