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Endothelin and endothelin antagonism: roles in cardiovascular health and disease
P Tamirisa1, W H Frishman, A Kumar
1Department of Medicine, Albert Einstein College of Medicine-Montefiore Medical Center, Bronx, NY 10461, USA.
Insights
Endothelin, a potent vasoconstrictor, influences vascular tone and mitogenesis. Its antagonists show promise for treating various cardiovascular diseases and understanding endothelin
Area of Science:
- Cardiovascular Physiology and Pharmacology
- Endothelin Signaling Pathways
Background:
- Endothelin is identified as the most potent mammalian vasoconstrictor.
- It comprises three isoforms that regulate vascular tone and mitogenesis.
- These isoforms interact with ETA and ETB receptor subtypes, mediating diverse physiological actions across multiple organ systems.
Purpose of the Study:
- To explore the physiological roles of endothelin and its receptor subtypes.
- To investigate endothelin's involvement in various cardiovascular and systemic diseases.
- To assess the therapeutic potential of endothelin antagonists and ECE inhibitors.
Main Methods:
- Review of existing literature on endothelin physiology and pharmacology.
- Analysis of the mechanisms of action for endothelin receptor antagonists and ECE inhibitors.
- Examination of the impact of existing cardiovascular drugs on endothelin activity.
Main Results:
- Endothelin isoforms (ETA and ETB) are crucial in vascular tone and mitogenesis.
- Endothelin is implicated as a disease marker or etiological factor in conditions like hypertension, heart failure, and atherosclerosis.
- Developed antagonists and inhibitors effectively interfere with endothelin function.
Conclusions:
- Endothelin antagonists hold significant therapeutic potential for a broad range of diseases.
- These antagonists can serve as valuable biologic probes for elucidating endothelin's actions in humans.
- Further research into endothelin pathways may lead to novel treatment strategies for cardiovascular pathologies.
Abstract:
Endothelin is the most potent mammalian vasoconstrictor yet discovered. Its three isoforms play leading roles in regulating vascular tone and causing mitogenesis. The isoforms bind to two major receptor subtypes (ETA and ETB), which mediate a wide variety of physiologic actions in several organ systems. Endothelin may also be a disease marker or an etiologic factor in ischemic heart disease, atherosclerosis, congestive heart failure, renal failure, myocardial and vascular wall hypertrophy, systemic hypertension, pulmonary hypertension, and subarachnoid hemorrhage. Specific and nonspecific receptor antagonists and ECE inhibitors that have been developed interfere with endothelin's function. Many available cardiovascular therapeutic agents, such as angiotensin-converting-enzyme inhibitors, calcium-entry blocking drugs, and nitroglycerin, also may interfere with endothelin release or may modify its activity. The endothelin antagonists have great potential as agents for use in the treatment of a wide spectrum of disease entities and as biologic probes for understanding the actions of endothelin in human beings.