Orbol ester potentiation of canine pulmonary vasoreactivity to
histamine.
Ikeda, Scott A. Barman Stephen R.
Department of Pharmacology, and Toxicology, Medical College of
Georgia, Augusta, Georgia 30912
APStracts 2:0110A, 1995.
The effect of phorbol myristate acetate (PMA) on canine pulmonary
vasoreactivity to histamine was determined in the isolated blood
perfused dog lung. Pulmonary vascular resistances and compliances
were measured using vascular occlusion techniques. Histamine (10-5 M)
significantly increased postcapillary resistance by venoconstriction,
and significantly attenuated total vascular compliance by decreasing
large vessel compliance and middle compartment compliance.
Pretreatment with the phorbol ester PMA (10-7 M) significantly
potentiated the vasoactive response to histamine and elicited an
edemagenic effect in the isolated dog lung through modulation of the
histaminergic vasoconstrictor effect on precapillary resistance,
postcapillary resistance, and pulmonary vascular compliance.
Pretreatment with the protein kinase C inhibitors staurosporine (10-7
M) and calphostin C (10-6 M), and the dihydropyridine calcium (Ca2+)
channel blocker nifedipine (10-5 M) significantly attenuated the
effect of PMA on histaminergic mediated vasoconstriction. The results
of this study indicate that phorbol esters may exert their effect on
canine pulmonary vasoreactivity predominantly through activation of
protein kinase C and influx of Ca2+ through voltage dependent Ca2+
channels.
Received 14 September 1994; accepted in final form 27 February
1995.
APS Manuscript Number A963-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.