Endothelin Levels and blood pressure fall in response to the removal of a malignant haemangioendothelioma which is a rare tumour thought to release endothelins.
- They are produced within the vascular endothelium
- Endothelin 1 (ET1) is a 21 amino acid peptide formed from a 39 AA precursor (Big ET1).
- There are 3 isoforms. The roles of ET2 and ET3 are less clear
- Endothelin 1 is the most potent vasoconstrictor known.
- Acts upon the underlying smooth muscle and causes vasoconstriction
Stimulus to release
- Hypoxia, Adrenaline [US Epinephrine]
- Cortisol and Angiotensin II
- Shear stress and Insulin and Ciclosporin
Release Inhibited by
- Nitric oxide, ANP, PGI2, PGE2
- Potent vasoconstrictors - intense vasoconstriction of coronary vessels
- Contracts vascular smooth muscle
- Positive inotropic and chronotropic effects on the heart
- There are at least two different ET-1 receptors - namely ETA and ETB.
- Both of these receptors are coupled to a Gq-protein and the formation of IP3. Increased IP3 causes calcium release by the sarcoplasmic reticulum, which causes smooth muscle contraction. In blood vessels, the ETA receptor is dominant under normal conditions in terms of ET-1 effects on contraction.
- ETA is present on vascular smooth muscle cells and not on the endothelium and causes vasoconstriction.
- ETB is found on both vascular smooth muscle cells and on endothelium and causes the release of NO and may inhibit apoptosis.