Influence of the phospholipase-c and myosin light chain kinase
inhibitors, u73122 and kt 5926, and the role of l-calcium channels on
vasoconstrictor responses in the pulmonary vascular bed of the
cat.
Kaye, Alan D., Bobby D. Nossaman, Ikhlass N. Ibrahim, and Philip J.
Kadowitz.
Departments of Anesthesiology and Pharmacology, Tulane University
Medical Center, New Orleans, Louisiana 70112-2699
APStracts 2:0123L, 1995.
The effects of U73122, a phospholipase C inhibitor, on pressor
responses to angiotensin II (Ang II), norepinephrine (NE), serotonin
(5-HT), 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 the calcium channel opener, 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 U73122, a phospholipase C inhibitor, into the perfused
lobar artery at 10-100 [mu]g/kg for 10 minutes significantly reduced
responses to Ang II, serotonin, and NE, however, U73122 did not alter
responses to Bay K 8644 or to U46619. In a separate series of
animals, the effects of the myosin light chain kinase inhibitor, KT
5926, were investigated and following infusion of KT 5926 into the
perfused lobar artery at 1-2 [mu]g/kg for 10 minutes responses to Ang
II, NE, 5-HT, Bay K 8644, and U46619 were reduced significantly. In a
final series of experiments, the effects of the L-type calcium
channel blocker, nicardipine, were investigated and infusion of the
L-type calcium channel blocker into the perfused lobar artery at 0.5
-1 [mu]g/kg for 10 minutes reduced responses to Ang II, Bay K 8644,
and to NE. However, nicardipine did not alter pressor responses to 5
-HT, or the thromboxane A2 mimic, U46619. Nicardipine, when combined
with the phospholipase inhibitor, U73122, significantly reduced
responses to Ang II, NE, 5-HT, and Bay K 8644, whereas there was no
significant change in pressor responses to the thromboxane A2 mimic,
U46619. These data provide support for the hypothesis that pulmonary
pressor responses to Ang II, 5-HT, and NE are mediated, in part, by
the activation of phospholipase C and calcium entry through L-type
channels. These data also suggest that pulmonary responses to Ang II,
NE, 5-HT, and U46619 are mediated in part by the activation of myosin
light chain kinase in the pulmonary vascular bed of the cat.
Received 21 February 1995; accepted in final form 8 May 1995.
APS Manuscript Number L51-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.