Endothelins

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 Endothelins

• Since its discovery in the late 1980’s the

endothelium-derived peptide endothelin-1
(ET-1) has been suggested to play a role in
maintenance of systemic vascular tone.
• Endothelins are a family of 21-amino acid
peptides (ET-1,ET-2 and ET-3)
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 Endothelin Receptors
• ETA receptor

They are preferentially activated by ET1, is expressed

predominately in vascular smooth muscle cells and the
myocardium. When activated, will generally produce
vasoconstriction.
• ETB receptors

They are expressed on both endothelium and smooth

muscle cells and when activated will promote vasodilation.
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• Changes in the level of ET-1 and endothelin
receptor gene expression may play a significant
role in the development of essential hypertension,
pulmonary hypertension and heart disease.
• Overall physiological effect of ET-1 seems to be an
increase in blood pressure.
• In the CV system, ET-1 enhances positive inotropic
and chronotropic effects.

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 Diseases and Conditions Associated with
Elevated Endothelin
• Because of its powerful vasoconstrictor properties, and its effects on
intracellular calcium, ET-1 has been implicated in the pathogenesis of
• Hypertension

• Coronary vasospasm

• Heart failure

• In the latter condition, ET-1 can contribute to calcium overload and

hypertrophy.
• Endothelin receptor antagonists have been shown to decrease mortality
and improve hemodynamics in experimental models of heart failure.

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 Antagonists

• ET receptor antagonists (e.g. Bosentan);

– Have been shown to have beneficial effects on
both cardiac hypertrophy and symptoms of
congestive heart failure

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