EFFECTS OF PHOSPHOLIPASE A(2), 12-LIPOXYGENASE, AND CYCLOOXYGENASE INHIBITORS IN THE FELINE PULMONARY BED

The effects of phosphonofluoridic acid, methyl-5,8,11,14-eicosatetraen yl ester (MAFP), a phospholipase A(2) inhibitor, on presser responses to angiotensin II (ANG 11), norepinephrine (NE), serotonin (5-HT), the calcium channel opener BAY K 8644, and the thromboxane A(2) mimic U-4 6619 were studied in the pulmonary vascular bed of the intact-chest ca t. 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 perf used lobar artery at doses of 100 to 300 mu g/kg for 10 min significan tly reduced vasoconstrictor responses to ANG II; however, the phosphol ipase A(2) inhibitor did not alter vasoconstrictor responses to BAY K 8644, 5-HT NE, or U-46619. The combination of the higher dose of the p hospholipase A(2) inhibitor MAFP with the phospholipase C inhibitor U- 73122 significantly affected vasoconstricter responses to ANG II, NE, and 5-HT but not to BAY K 8644. In a separate series of animals, the e ffects of a lipoxygenase inhibitor, baicalein, were investigated. Infu sion of baicalein into the perfused lobar artery at doses of 100 mu g/ kg for 10 min significantly reduced vasoconstrictor responses to ANG I I 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 cyclooxygena se inhibitor, meclofenamate, were investigated, and intravenous inject ion 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 va sopressor responses to ANG II are mediated, in part, by the activation of phospholipase A(2), phospholipase C, and the lipoxygenase pathway in the pulmonary vascular bed of the cat.