EFFECTS OF BLOOD ON CEREBRAL VASCULAR MUSCLE REACTIVITY

Project: Research project

Description

The aim of this proposal is to determine the causes and cellular mechanisms
responsible for increased sensitivity of cerebral blood vessels chronically
exposed to extraluminal blood. Two methods will be used for chronic
exposure of rabbit basilar arteries to blood. Blood will be injected into
the subarachnoid space of rabbits to simulate subarachnoid hemorrhage.
Rabbit basilar arteries will also be implanted in the anterior eye chamber
of host animals and the implants exposed to blood by blood injections into
the anterior chamber containing the implant. In vitro dose-response curves
for vasoconstrictors and vasodilators and the response to nerve stimulation
will be compared in blood-free and blood-exposed arterial segments.
Intracelluar membrane potential will be recorded and calcium dependent
electrical spike activity analyzed in control and blood-exposed cerebral
vessels. These techiques will be used in experiments designed to determine
the causes and mechanisms of blood-induced supersensitivity of rabbit
basilar arteries. The time course for development of supersensitivity will
be described to determine the time for onset of the phenomenon and whether
it is transient or maintained. Sympathetically denervated cerebral
arteries exposed to blood will be used to separate direct effects of blood
on vascular muscle sensitivity from indirect blood-induced sympathetic
denervation effects on vascular muscle. A possible reduced relaxation
response of blood-exposed arteries to vasodilators will also be
investigated. The cellular mechanisms responsible for altered vascular
reactivity will also be studied. Membrane depolarization and the effects
of ouabain on electrical and mechanical activity will be investigated to
explore the role of inhibition of the vascular Na+ K+ pump as a cause of
blood-induced supersensitivity. Alterations in calcium movements will be
examined by measuring electrically induced spike activity in the presence
of tetraethylammonium. Arteries implanted in the anterior eye chamber and
exposed to blood will be studied so that eventaully human cerebral arteries
can be implanted and effects of blood investigated. It is hoped that a
better understanding of the effects of blood on cerebral arteries will lead
to more effective therapy for blood-induced cerebrovasospasm.
StatusFinished
Effective start/end date4/1/836/30/86

Funding

  • National Institutes of Health

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Blood Vessels
Muscles
Basilar Artery
Arteries
Anterior Chamber
Rabbits
Vasodilator Agents
Subarachnoid Space
Tetraethylammonium
Cerebral Arteries
Calcium Signaling
Vasoconstrictor Agents
Ouabain
Subarachnoid Hemorrhage
Membrane Potentials