The strong contractile effect of the thromboxane receptor agonist U-46619 in isolated human pulmonary arteries and its competitive antagonism by BM-13.505

Ring segments (I mm in diameter) of the pulmonary artery obtained from 16 patients undergoing thoracic surgery were mounted in tissue baths. Cumulative concentration-response curves of some prostanoids and amines were obtained, and Emax and pEC50 values calculated. Noradrenaline, phenylephrine, clonidine and serotonin (5-HT) showed low intrinsic activities. Prostaglandin F2 alpha (PGF2 alpha) induced strong contractions with an Emax of 126% of the preceding K+ (124 mM)-induced contraction, but its potency was low (pEC50 = 5.70). The thromboxane receptor agonists U-46619 and U-44069 induced strong contractions (Emax = 139% and 133% respectively) and were significantly more potent than the other drugs used (pEC50 = 8.43 and 8.30 respectively). The thromboxane receptor antagonist BM-13.505 (10(-8) to 10(-6) M) caused rightward parallel shifts of the U-46619 concentration-response curves without reduction of Emax, indicating competitive antagonism.