Repeated cocaine administration reduces bradykinin-induced dilation
of pial arterioles.
Copeland, J. R., K. A. Willoughby, R. J. Police, and E. F. Ellis.
Department of Pharmacology and Toxicology, Medical College of
Virginia, Virginia Commonwealth University, Richmond, Virginia 23298
-0613
APStracts 3:0265H, 1996.
Using the acute cranial window technique in rabbits under surgical
anesthesia, we tested the vasoactivity of acetylcholine (ACh, 10-8 -
10-5 M), bradykinin (BK, 10-8 - 10-5 M) and asphyxia (10% O2, 9% CO2)
following subchronic pretreatment with cocaine. Following repeated
administration of cocaine (20 mg/kg/day x 7 days, sc) the BK-induced
dilation of pial arterioles was reduced by 51%. Previous work has
shown that BK produces dilation of pial arterioles by a
cyclooxygenase-dependent oxygen radical-mediated mechanism and that
in rabbits the BK-induced dilation is dependent on both vascular and
non-vascular cyclooxygenase. Selective blockade of vascular
cyclooxygenase, in addition to cocaine treatment, did not produce any
greater inhibition of the BK-induced dilation. The dilation in
response to ACh and asphyxia were unaltered by cocaine. Levels of CSF
prostaglandins suggest cocaine pretreatment may inhibit cerebral
vascular prostaglandin production. Together, CSF prostaglandin and
vasoreactivity data indicate cocaine pretreatment selectively
inhibits the vascular cyclooxygenase-dependent mechanism mediating
the BK-induced dilation. This decreased response to BK in cocaine
-treated rabbits may result from decreased oxygen radical production
concomitant with decreased vascular prostaglandin production.
Alternatively, oxygen radical scavenging may be increased following
cocaine treatment. We speculate that cocaine-induced alterations in
cerebrovascular function and metabolism may be related to the
increased incidence of stroke reported to occur in human cocaine
users.
Received 23 August 1994; accepted in final form 13 February 1996.
APS Manuscript Number H761-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96