Aldosterone breakthrough during RAS blockade: a role for endothelins and their antagonists?
Activation of the renin-angiotensin system (RAS), with ensuing aldosterone excess, detrimentally affects outcome in patients with hypertension and heart failure (HF). RAS blockade with angiotensin (Ang) 1-converting enzyme inhibitors (ACEIs) or Ang II type 1 receptor blockers (ARBs) is beneficial in such conditions. However, aldosterone secretion can persist despite these treatments. Hence, mechanisms besides Ang II acquire the role of aldosterone secretagogue. The RALES and EPHESUS studies have shown that this aldosterone "escape" or "breakthrough" is an important factor, because it is a determinant of outcome in HF patients. Endothelin (ET)-1, which stimulates aldosterone secretion via both A (ETA) and B (ETB) receptor subtypes, and which is increased in HF, is a candidate for the "aldosterone breakthrough." Moreover, the novel ET peptide ET-1(1-31) is involved in adrenocortical growth. Therefore, findings suggesting a role for the ET-1 system as an aldosterone secretagogue, along with the potential usefulness of endothelin antagonists for the prevention of "aldosterone breakthrough," are discussed.
Rossi
Gian Paolo
GP
DMCS-Internal Medicine 4, University Hospital, via Giustiniani, 2, 35126 Padova, Italy. gianpaolo.rossi@unipd.it
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D017466:Receptors, Endothelin; D000450:Aldosterone