From the Guidelines
Endothelin peptides are primarily located in the vascular endothelial cells, where they are produced and play a crucial role in regulating vascular tone and blood pressure. These peptides are also found in various other tissues and organs, including the heart, kidneys, lungs, brain, and adrenal glands 1. Endothelins are synthesized as larger precursor molecules (preproendothelins) within the endothelial cells and are then processed into their active forms before being released. Once secreted, they act locally on nearby smooth muscle cells and other target tissues. There are three main isoforms of endothelin (ET-1, ET-2, and ET-3), with ET-1 being the most abundant and physiologically significant, as demonstrated in a study published in the European Heart Journal in 2004 1.
Key Points
- Endothelin peptides are potent vasoconstrictors and mitogens for smooth muscle cells
- They bind to two types of receptors, ETA and ETB, which are found in smooth muscle cells and endothelial cells, respectively
- Activation of ETA and ETB receptors on smooth muscle cells mediates the vasoconstrictive and mitogenic effects of ET-1, as supported by a study published in 2016 1
- Stimulation of endothelial ETB receptors promotes ET-1 clearance and activation of NO and prostacyclin release
- Dysregulation of endothelin production and activity is implicated in several cardiovascular disorders, including hypertension, heart failure, and pulmonary arterial hypertension.
Location and Function
Endothelin peptides are primarily located in the endothelial cells that line blood vessels throughout the body. They play crucial roles in regulating vascular tone, blood pressure, and tissue perfusion. Their production increases in response to various stimuli, including hypoxia, shear stress, and inflammatory cytokines.
Clinical Significance
The endothelin system has been demonstrated to be activated in both plasma and lung tissue of PAH patients, supporting a prominent role for the endothelin system in the pathogenesis of PAH, as reported in a study published in the European Heart Journal in 2016 1. Therefore, endothelin receptor antagonists are a potential therapeutic option for the treatment of PAH, as they can block the vasoconstrictive and mitogenic effects of ET-1.
From the Research
Location of Endothelin Peptides
- Endothelin peptides are produced by a variety of tissues, including the endothelium in the human cardiovascular system 2
- The main endothelin produced by the endothelium is ET-1, which is primarily a locally acting paracrine substance 2, 3
- Endothelin-1 is generated mainly by vascular endothelial cells and exerts various important biological actions, mediated by two receptor subtypes, ET-A and ET-B 4, 5
- Endothelin peptides are also produced in other tissues, including the heart, where they play a role in regulating vascular tone and blood pressure 5
- ET-1 is overexpressed in the vascular wall of certain models of hypertension, such as salt-dependent models of hypertension, and in stroke-prone spontaneously hypertensive rats 3
Specific Locations
- Endothelin-1 is produced by the endothelium in the human cardiovascular system, including in coronary arteries 3
- ET-1 is also expressed in the endothelium of subcutaneous resistance arteries in moderate to severe hypertensive patients 3
- Endothelin peptides are found in various human tissues, including cardiac tissue, where they play a role in maintaining vascular tone and blood pressure 4, 5