AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 532-L538, Copyright © 1995 by American Physiological Society
Influence of protein kinase C inhibitors on vasoconstrictor responses in the pulmonary vascular bed of cat and rat
A. D. Kaye, B. D. Nossaman, I. N. Ibrahim, C. J. Feng and P. J. Kadowitz
Department of Anesthesiology, Tulane University Medical Center, New Orleans, Louisiana 70112-2699.
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, norepinephrine (NE), serotonin, and U-46619
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
micrograms/kg for 10 min 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 U-46619. 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 micrograms/kg for
10 min also reduced pressor responses to the angiotensin peptides and to NE
and did not alter pressor responses to serotonin or to U-46619. 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 after administration of 20
micrograms ia of the PKC inhibitor staurosporine. (ABSTRACT TRUNCATED AT
250 WORDS)
