Prostacyclin and thromboxane A2 synthesis by rabbit pulmonary artery.
Superfused spiral strips of rabbit intrapulmonary artery (i.p.a.) were contracted by arachidonic acid (AA) and by the following substances in order of potency: prostaglandin (PG) endoperoxide analog (U46619) > PGH2 > PGF2 alpha. Intrapulmonary artery strips were consistently relaxed by PGE2 and by the enzyme inhibitors, indomethacin, aspirin, meclofenamic acid and 1-pentylimidazole. These latter inhibitors of cyclooxygenase and thromboxane (TX) synthetase also blocked the AA-induced contraction of rabbit i.p.a. Prostacyclin had no effect on the i.p.a. or produced either a small contraction or relaxation. TXA2, formed by incubating horse platelet microsomes with PHG2, always contracted the tissue and was more potent than the parent endoperoxide. Incubations of [14C]AA with i.p.a. produced mainly [14C]-6-keto-PGF1 alpha (he breakdonw product of prostacyclin ) and [14C]TXB2 (the breakdown product of TXA2); the identities of these products were confirmed by radioimmunoassay and by gas chromatography-mass spectrometry. The synthesis of TXB2 by i.p.a. cannot be attributed to adhering lung tissue or platelets and appears to be produced by the vascular tissue itself. It is concluded that, although both prostacyclin and thromboxane may contribute to the resting tone of the rabbit i.p.a., the response to AA is mainly due to production of TXA2.
D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D011464:Epoprostenol / Q000096:biosynthesis*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D011463:Prostaglandins H; D013931:Thromboxanes; D013928:Thromboxane A2; D011464:Epoprostenol