Unusual pulmonary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with endoperoxides and other prostanoids.
Microsomes from stomach fundus and blood vessels transform the endoperoxide, PGH2, into a newly discovered unstable substance, PGI2, that relaxes arterial strips and inhibits platelet aggregation. 13,14-Dehydro-PGI2 methyl ester, a newly synthesized, stable PGI2 analog, was found to have potent vasodilator activity in the feline and simian pulmonary vascular bed. The PGI2 analog decreased lobar arterial perfusion pressure in the intact cat and monkey. Because pulmonary blood flow was held constant and left atrial pressure was unchanged, the decrease in perfusion pressure reflects a decrease in pulmonary vascular resistance. The dilator response was unusual in that it persisted for 10-12 min, whereas the response to PGE1, the only other vasodilator prostaglandin in the mature animal, persisted for only 1-2 min. The dilator response to the PGI2 analog was enhanced when pulmonary vascular resistance was increased. This substance had less effect on cardiac output and aortic pressure than PGE1, whereas it was a more potent pulmonary vasodilator. These data demonstrate that prostacyclin-like substances possess novel vasodilator activity in the pulmonary circulation and suggest a therapeutic use in the treatment of pulmonary hypertensive diseases.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D000882:Haplorhini; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011463:Prostaglandins H; D011465:Prostaglandins, Synthetic; D014665:Vasodilator Agents; C026435:13,14-dehydroprostaglandin I2 methyl ester; D011464:Epoprostenol