Influence of brain injury on vasopressin-induced pial artery
vasodilation: role of superoxide anion.
Armstead, W. M.
Departments of Anesthesia and Pharmacology, The University of
Pennsylvania and The Children's Hospital of Philadaelphia,
Philadelphia, PA 19104-4399
APStracts 2:0375H, 1995.
The present study was designed to investigate the effect of fluid
percussion brain injury on vasopressin induced pial artery
vasodilation and the role of superoxide anion generation in those
observed effects. In the piglet, it has been previously observed that
brain injury produces pial artery constriction associated with free
radical generation using nitroblue tetrazolium as an index of
superoxide anion formation. Anesthetized newborn pigs equipped with a
closed cranial window were connected to a percussion device
consisting of a saline-filled cylindrical reservoir with a metal
pendulum. Brain injury of moderate severity (1.9-2.3 atm) was
produced by allowing the pendulum to strike a piston on the cylinder.
Cortical periarachnoid CSF was collected from beneath the window for
assay of cGMP. Topical administration of vasopressin in physiologic
and pharmacologic concentrations (10 and 1000 [mu]U/ml) produced
vasodilation that was reversed to constriction following brain injury
(15+1 vs -8+1 and 25+1 vs -13 +1% for 10 and 1000 [mu]U/ml before and
after injury, respectively). Vasopressin-induced dilation was
associated with increased cortical periarachnoid CSF cGMP and these
biochemical changes were blunted by brain injury (407+12 and 720+28
vs 268+4 and 272+5 f mol/ml for control and 10 [mu]U/ml before and
after injury, respectively). Vasopressin-induced pial dilation was
also attenuated by the nitric oxide synthase inhibitor L-NNA (10-6M)
(12+1 vs 2+1 and 22+2 vs 5+1% for 10 and 1000 [mu]U/ml before and
after L-NNA, respectively). Biochemical changes associated with
vasopressin dilation were also similarly attenuated by L-NNA. In
contrast, PEG-SOD and catalase (1000 and 10,000 U/Kg, respectively)
pretreatment 30 min prior to injury partially restored vasopressin
-induced pial artery dilation (14+1 vs 3+1 and 22+1 vs 2+4% for 10 and
1000 [mu]U/ml before and after injury, respectively). Similarly,
biochemical changes associated with vasopressin dilation were also
partially restored by PEG-SOD and catalase following injury. These
data show that vasopressin is reversed from a dilator to a
vasoconstrictor following brain injury. Further, these data suggest
that superoxide anion generation contributes to the alteration of
vasopressin cerebrovascular effects following injury. Finally, these
data suggest that such altered vasopressin cerebrovascular effects
contribute to pial vasoconstriction following brain injury.
Received 30 May 1995; accepted in final form 21 August 1995.
APS Manuscript Number H495-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.