Expansion
Nitric oxide and prostacyclin dilate; endothelin and thromboxane constrict
Expansion
Vasodilators
- Nitric oxide - produced from L-arginine by endothelial nitric oxide synthase in response to shear stress and to acetylcholine, bradykinin and histamine. Acts through cyclic GMP; also inhibits platelet aggregation
- Prostacyclin (PGI2) - vasodilator and inhibitor of platelet aggregation
- Endothelium-derived hyperpolarising factor
Vasoconstrictors
- Endothelin-1 - the most potent endogenous vasoconstrictor known
- Thromboxane A2 - vasoconstrictor and promoter of platelet aggregation
- Angiotensin II, generated locally by endothelial ACE
The healthy endothelium favours the dilator, antithrombotic side. Endothelial dysfunction, as in hypertension, diabetes, smoking and hyperlipidaemia, reduces nitric oxide availability and tips the balance towards vasoconstriction, thrombosis and inflammation; it is the earliest measurable step in atherosclerosis.
Drug relevance: nitrates and sildenafil act on the nitric oxide pathway, aspirin inhibits thromboxane, and bosentan blocks endothelin receptors in pulmonary hypertension.