Although endothelin A receptor (ETA) antagonists are approved for the treatment of pulmonary hypertension, their clinical utility in other diseases has been limited by fluid retention. ETA blocker-induced fluid retention could be attributed to inhibition of ETA in the heart, vasculature, and/or kidney. Mice were generated with the absence of ETA, specifically in cardiomyocytes, smooth muscle, the nephron, or the collecting duct. Administration of ETA antagonists caused fluid retention in control mice on a high salt diet and in mice with heart ETA knockout. In contrast, mice with smooth muscle ETA knockout had reduced fluid retention, and mice with nephron or collecting duct ETA disruption had no fluid retention after ETA blockade. These findings suggest that ETA antagonist-induced fluid retention is attributed to a direct effect on the collecting duct and partially related to their vascular action.
See article at J Pharmacol Exp Ther 2013, 346:182–189.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics