Prostanoid action on the human pulmonary vascular system

1. Four types of prostanoid receptor are present an pulmonary arterial vessels of man. Thromboxane (TP) receptors mediate constriction and are blocked by antagonists such as BAY u-3405, GR 32191 and EP 169. Prostaglandin (PG) EP3 receptors also mediate constriction, the agonist potency ranking being SC 46275>sulprostone>misoprostol greater than or equal to PGE(2); this action needs to be borne in mind when PGE analogues are used therapeutically. 2. Prostaglandin E-2 causes relaxation in a few pulmonary artery preparations: an EP2 receptor may be involved. Prostacyclin, acting through IP receptors, consistently produces relaxation and studies are in progress to determine the contribution made by K+-channel opening. Agonist potencies of stable prostacyclin analogues and non-prostanoid prostacyclin mimetics, such as BMY 45778 and the novel diphenylindole CU 23, on human pulmonary artery and platelets are well correlated. Interestingly, the non-prostanoid mimetics show persistent relaxant effects in vitro, which may be related to their high lipophilicities. 3. Prostacyclin and iloprost are being used to treat severe pulmonary hypertension; further study of the pharmacodynamic and pharmacokinetic properties of other IP receptor agonists could produce improved therapy.