prostacycline

Prostacyclin, or prostaglandin I2 (PGI2), is a member of the prostanoid family and a potent lipid mediator produced mainly by vascular endothelial cells. It is derived from arachidonic acid via the cyclooxygenase pathway to the intermediate prostaglandin H2 (PGH2), which is then converted by prostacyclin synthase to PGI2. Prostacyclin is chemically unstable with a very short half-life in the circulation, and it is rapidly hydrolyzed to the inactive metabolite 6-keto-PGF1α, commonly measured as a surrogate marker of prostacyclin production.

In terms of mechanism, prostacyclin binds the prostacyclin receptor (IP receptor), triggering an increase in intracellular cyclic AMP. In vascular smooth muscle, this promotes vasodilation; in platelets, it inhibits aggregation. Through these actions, prostacyclin helps maintain vascular tone and prevents unwanted clotting, balancing the effects of thromboxane A2.

Clinical relevance: Prostacyclin and its analogs are used in the treatment of pulmonary arterial hypertension. Epoprostenol, iloprost, and treprostinil mimic prostacyclin activity and can be given by continuous IV infusion or inhalation, depending on the agent. Due to rapid inactivation, native PGI2 is not typically used therapeutically; synthetic analogs have longer half-lives and practical dosing regimens. Side effects include flushing, jaw pain, headache, hypotension, and edema, and there is an elevated risk of bleeding when used with anticoagulants or antiplatelets. Measurement of 6-keto-PGF1α in plasma or urine can reflect prostacyclin production.