The effects of inhibition of phospholipase a2, 12-lipoxygenase and
cyclooxygenase on vasoconstrictor responses in the pulmonary vascular
bed of the cat.
Kaye, Alan D., Bobby D. Nossaman, Donald E. Smith, Ikhlass N. Ibrahim,
John D. Imig, and Philip J. Kadowitz.
Departments of Anesthesiology and Pharmacology, Tulane University
Medical Center, New Orleans, Louisiana 70112-2699
APStracts 3:0144L, 1996.
The effects of phosphonofluoridic acid, methyl-,5,8,11,14
-eicosatetraenyl ester, 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, U46619, 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, U46619, and Bay K 8644, into the
lobar arterial perfusion circuit caused dose-related increases in
lobar arterial pressure which were reproducible with respect to time.
Infusion of phosphonofluoridic acid, methyl-,5,8,11,14
-eicosatetraenyl ester into the perfused lobar artery at doses of 100
-300?[mu]g/kg for 10 minutes 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 to
U46619. Combining the higher dose of the phospholipase A2 inhibitor
phosphonofluoridic acid, methyl-,5,8,11,14-eicosatetraenyl ester 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?[mu]g/kg for 10 minutes
significantly reduced vasoconstrictor responses to Ang II; but not
the vasoconstrictor responses to Bay K 8644, 5-HT, NE, or U46619. 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
U46619. 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 by the
activation of the lipoxygenase pathway in the pulmonary vascular bed
of the cat.
Received 8 November 1995; accepted in final form 19 August 1996.
APS Manuscript Number L321-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996