Endothelin ETB1 receptor agonism as a new therapeutic strategy in pulmonary arterial hypertension and chronic heart failure.

Abstract

Pulmonary arterial hypertension and post-ischemic chronic heart failure are highly prevalent diseases with high morbidity and mortality rates due to chronic vascular injury and extensive remodeling responses at the level of the vessel walls. Endothelins play a central role in this setting, through a complex signaling system that mainly affects endothelial and vascular smooth muscle cells. ETA and ETB2 endothelin receptors are thought to mediate pro-ischemic responses, while ETB1 receptor activity could account for the overall protective effect of ETB signaling in physiology. The pharmacologic modulation of the endothelin system has mainly focused on the dual non-selective blockade of ETA and ETB endothelin receptors or to the selective blockade of ETA-related pathways to date. Good clinical results were achieved in the setting of pulmonary hypertension but no advantage has been demonstrated for heart failure. Restoring and enhancing the physiological protective role of ETB1-signaling with concomitant blockade of ETB2 could possibly improve the efficacy of current therapies in the setting of pulmonary arterial hypertension and post-ischemic chronic heart failure.

• Authors: Giuseppe A Ramirez
• Journal: Medical hypotheses (Med Hypotheses) Vol. 81 Issue 5 Pg. 896-7 (Nov 2013) ISSN: 1532-2777 [Electronic] United States
• PMID: 23962965 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Receptor, Endothelin B

Topics

• Drug Delivery Systems
• Familial Primary Pulmonary Hypertension
• Heart Failure (drug therapy)
• Humans
• Hypertension, Pulmonary (drug therapy)
• Models, Biological
• Receptor, Endothelin B (agonists, metabolism)
• Signal Transduction (physiology)