title: Pharmacology of prostaglandins in the pulmonary microcirculation.
abstract: In unanesthetized sheep, arachidonate infusion increases lung microvascular pressure and augments pulmonary transvascular filtration without altering lung vascular permeability. Pulmonary vascular effects of arachidonate are caused by its conversion to highly active cyclooxygenase products, including PGH2 and, perhaps, thromboxane A2. Cyclooxygenase blockers inhibit pulmonary vascular actions of arachidonate. Most prostaglandins derived from PGH2 [i.e., PGB2, PGD2, PGE, and PGF2 alpha] are vasoconstrictors that exhibit potency intermediate between PGH2 and arachidonate. Vasoconstrictor prostaglandins cause increased flow of protein-poor lung lymph with no indication of altered lung vascular permeability. Vasodilator prostaglandins [i.e., PGE1, PGI2] cause changes in lung lymph formation that are not explained by microvascular hydrostatic-pressure effects alone. Whether lung lymph responses to PGE1 and PGI2 resulted from changes in perfused pulmonary vascular surface area or vascular permeability effects was tested with infusions during near-maximal pulmonary vascular recruitment with increase pressure. Maintaining mechanically increased left atrial pressure constant should minimize changes in lung lymph formation due to pulmonary vascular recruitment and derecruitment, and exaggerate lymph responses due to changes in vascular permeability. When infused during mechanically increased pressure, PGE1 and PGI2 produce similar pressure-mediated decreases in steady-state lung lymph flow, despite increases in pulmonary blood flow, heart rate, and respiratory rate with PGI2 and not with PGE1. In conclusion, PGE1 and PGI2 cause hemodynamic changes that can increase [PGI2] or decrease [PGE1] lung lymph flow. Prostaglandins do not directly alter lung vascular permeability.
mesh_terms: D000527:Alprostadil; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep
chemical_list: D001095:Arachidonic Acids; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D011463:Prostaglandins H; D011464:Epoprostenol; D000527:Alprostadil