Influence of protein kinase c inhibitors, staurosporine and calphostin c,
on vasoconstrictor responses in the pulmonary vascular bed of the cat and the
rat.
Kaye, Alan D., Bobby D. Nossaman, Ikhlass N. Ibrahim, Chang J. Feng, and
Philip J. Kadowitz.
Departments of Anesthesiology and Pharmacology, Tulane University Medical
Center, New Orleans, Louisiana 70112-2699
APStracts 2:0001L, 1995.
The effects of staurosporine and calphostin C, two different protein kinase C
(PKC) inhibitors, on pressor responses were studied in the pulmonary vascular
bed of the intact-chest anesthetized cat and the isolated rat lung. Under
conditions of constant lobar blood flow in the cat, injections of the
angiotensin peptides, NE, serotonin, and U46619 into the lobar arterial
perfusion circuit caused dose related increases in lobar arterial pressure
and responses were reproducible with respect to time. Infusion of
staurosporine into the perfused lobar artery at 1-2 [mu]g/kg for 10 minutes
reduced the pressor response to the angiotensin peptides and to NE, however,
staurosporine did not alter pressor responses to serotonin or to the
thromboxane mimic, U46619. In a separate series of experiments, the effects
of calphostin C were investigated and infusion of the PKC inhibitor into the
perfused lobar artery at 1-5 [mu]g/kg for 10 minutes also reduced pressor
responses to the angiotensin peptides and to NE and did not alter pressor
responses to serotonin or to U46619. In the isolated rat lung, the inhibitory
effects of staurosporine on pulmonary pressor responses were investigated and
injections of angiotensin II, NE, and serotonin produced dose-related
increases in pulmonary arterial perfusion pressure that were decreased
following administration of the PKC inhibitor, staurosporine, in a dose of 20
[mu]g ia. The data provide support for the hypothesis that vasoconstrictor
responses to angiotensin peptides and NE in the pulmonary vascular bed are
mediated in part by the activation of PKC in the cat and in the rat; however,
responses to serotonin were inhibited only in the rat suggesting important
species differences in the mediation of the response to serotonin. The
present data suggest that pulmonary pressor responses to U46619 are not
mediated by the activation of PKC in the pulmonary vascular bed of the cat.
Received 30 August 1994; accepted in final form 6 January 1995.
APS Manuscript Number L254-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.