Endothelin

What is endothelin?

Endothelin (ET) is a natural peptide that helps manage your blood pressure by narrowing your blood vessels. This reduces blood flow through your vessels. Peptides are small proteins made up of short chains of amino acids.

Medical researchers first identified endothelin in 1987. Since then, they’ve uncovered many key functions of this peptide throughout your body. They’re also studying how excess endothelin can lead to several health issues, like heart failure and pulmonary hypertension.

What does endothelin do?

Endothelins are your body’s most powerful vasoconstrictor. Vasoconstriction is the process of narrowing your blood vessels to slow blood flow. This increases your blood pressure. Sometimes, a temporary increase in pressure is helpful to your body. But long-term high blood pressure causes health issues.

Scientists are studying many other roles of endothelins. Other than vasoconstriction, they also play a part in:

• Blood vessel structural changes (remodeling)
• Cognitive functioning
• Fetal development
• Immune system regulation
• Melanin production
• Nerve formation
• Ovulation
• Scar tissue formation (fibrosis)

Several situations can trigger the release of endothelin, including:

• A lack of oxygen in body tissues
• A release of hormones that manage blood pressure
• Injury and inflammation
• Pressure on your blood vessels, like during an angioplasty procedure

Most tissues throughout your body have endothelin receptors. Endothelin binds to these receptors to trigger various reactions.

Types

So far, scientists have found three types of endothelins. They all play a role in vasoconstriction, but some have other jobs. They include:

• Endothelin-1 (ET-1 or EDN1): This is the most common and strongest endothelin in your body. Its main job is vasoconstriction.
• ET-2 or EDN2: Your kidneys and intestines mainly make ET-2. This suggests it plays a role in regulating these organs. ET-2 also helps trigger ovulation.
• ET-3 or EDN3: ET-3 helps form certain nerves and produce cells that make melanin. It’s the pigment responsible for your skin, hair and eye color.

Where does endothelin come from?

The cells lining the inside of your blood vessels — the endothelium — mainly make endothelin. But other tissues contribute to its production, including:

• Brain cells
• Intestine cells
• Kidney cells
• Macrophages (immune system cells)
• Vascular smooth muscle cells

What conditions are related to endothelin?

Long-term elevated levels of endothelin can damage a variety of body tissues and organs. Healthcare providers call it endothelial dysfunction. Some examples of conditions it can cause include:

• Heart failure
• High blood pressure (hypertension)
• Certain cancers, especially ovarian cancer
• Post-menopausal hypertension (PMH)
• Preeclampsia
• Kidney disease, like diabetes-related nephropathy
• Pulmonary hypertension

What are endothelin receptor antagonists?

Endothelin receptor antagonists (ERAs) are medications that lower the amount of endothelin in your body. They bind to endothelin receptors and block endothelin from attaching and working. ERAs can help treat certain types of pulmonary hypertension. Researchers are also testing them for the treatment of immunoglobin A nephropathy (IgAN), a type of kidney disease.