Effects of phospholipase A2, 12-lipoxygenase, and cyclooxygenase inhibitors in the feline pulmonary bed.
The effects of phosphonofluoridic acid, methyl-5,8,11,14-eicosatetraenyl ester (MAFP), a phospholipase A2 inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), the calcium channel opener BAY K 8644, and the thromboxane A2 mimic U-46619 were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and BAY K 8644 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure that were reproducible with respect to time. Infusion of MAFP into the perfused lobar artery at doses of 100 to 300 microg/kg for 10 min significantly reduced vasoconstrictor responses to ANG II; however, the phospholipase A2 inhibitor did not alter vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. The combination of the higher dose of the phospholipase A2 inhibitor MAFP with the phospholipase C inhibitor U-73122 significantly affected vasoconstrictor responses to ANG II, NE, and 5-HT but not to BAY K 8644. In a separate series of animals, the effects of a lipoxygenase inhibitor, baicalein, were investigated. Infusion of baicalein into the perfused lobar artery at doses of 100 microg/kg for 10 min significantly reduced vasoconstrictor responses to ANG II but not the vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. In a final series of experiments, the effects of a cyclooxygenase inhibitor, meclofenamate, were investigated, and intravenous injection of the meclofenamate at a dose of 2.5 mg/kg did not significantly affect vasoconstrictor responses to ANG II, 5-HT, BAY K 8644, NE, or U-46619. These data provide support for the hypothesis that pulmonary vasopressor responses to ANG II are mediated, in part, by the activation of phospholipase A2, phospholipase C, and the lipoxygenase pathway in the pulmonary vascular bed of the cat.
Kaye
A D
AD
Department of Anesthesiology, Tulane University Medical Center, New Orleans, Louisiana 70112-2699, USA.
Nossaman
B D
BD
Smith
D E
DE
Ibrahim
I N
IN
Imig
J D
JD
Kadowitz
P J
PJ
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2; D011652:Pulmonary Circulation / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D004963:Estrenes; D044950:Flavanones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014662:Vasoconstrictor Agents; C104810:methyl arachidonylfluorophosphonate; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D008469:Meclofenamic Acid; C006680:baicalein; D001092:Arachidonate 12-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases