Effects of A23187, exogenous phospholipase A2 and exogenous arachidonic acid on pulmonary vascular resistance in isolated rabbit lung.
The authors gave infusions of exogenous arachidonic acid (AA), exogenous phospholipase A2 (PLA2) or A23187 into the pulmonary circulation of isolated salt-perfused rabbit lungs. Exogenous PLA2 and A23187 are agents that release the AA that is usually in the lung (i.e., endogenous pulmonary AA). The exogenous AA or A23187 led to pulmonary cyclooxygenase enzyme conversion of exogenous and endogenous AA to thromboxane A2 (TXA2), as TXB2, and prostacyclin, as 6-keto-prostaglandin-F1 alpha, as well as to elevations in pulmonary vascular resistance (PVR). The elevations in PVR as well as the elevations in TXB2 and 6-keto-prostaglandin-F1 alpha were prevented by indomethacin, a cyclooxygenase enzyme inhibitor, and the elevations in TXB2 and PVR but not the elevations in 6-keto-prostaglandin-F1 alpha were prevented by 1-benzylimidazole, a selective inhibitor of thromboxane synthesis. Maximum elevations in PVR occurred from conversion of AA to less than maximum levels of TXA2. Exogenous PLA2 led to release of endogenous AA with conversion to prostacyclin. However, such release of endogenous AA by exogenous PLA2 did not lead to conversion to TXA2 or to elevations in PVR. The authors conclude that elevations in PVR that depend on conversion of AA to TXA2 are limited by factors other than the amount of TXA2 or the amount of AA that is potentially available for such conversion.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology*; D066298:In Vitro Techniques; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D000001:Calcimycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2