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 a re blocked by antagonists such as BAY u-3405, GR 32191 and EP 169. Pro staglandin (PG) EP3 receptors also mediate constriction, the agonist p otency ranking being SC 46275>sulprostone>misoprostol greater than or equal to PGE(2); this action needs to be borne in mind when PGE analog ues are used therapeutically. 2. Prostaglandin E-2 causes relaxation i n a few pulmonary artery preparations: an EP2 receptor may be involved . Prostacyclin, acting through IP receptors, consistently produces rel axation and studies are in progress to determine the contribution made by K+-channel opening. Agonist potencies of stable prostacyclin analo gues and non-prostanoid prostacyclin mimetics, such as BMY 45778 and t he 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 hi gh lipophilicities. 3. Prostacyclin and iloprost are being used to tre at severe pulmonary hypertension; further study of the pharmacodynamic and pharmacokinetic properties of other IP receptor agonists could pr oduce improved therapy.