ENDOTHELIUM-DEPENDENT CONTRACTIONS &CEREBRAL VASOSPASM

Project: Research project

Project Details

Description

The causation of chronic spasm of the cerebral arteries following
subarachnoid hemorrhage is unknown. Exposure of the external surfaces of
cerebral arteries to blood products leads to the excessive production of
prostanoids associated with the generation of oxygen-derived free radicals.
The proposition to be tested is that oxygen-derived free radicals
particularly superoxide anions, released from endothelial cells, mediate
endothelium-dependent contractions by inactivation of endothelium-derived
relaxing factor(s), and contraction of smooth muscle either by direct
action or by production of prostanoids. The role of cyclooxygenase in
basal and stimulated production in endothelial cells of superoxide anions
will be determined, as will the effects of exogenously generated superoxide
anions on endothelial and smooth muscle cells. Experiments will be
conducted on isolated canine basilar arteries that had been subjected to
autologous venous blood injected into the cisterna magna. Endothelium-
dependent contractions will be analyzed in the presence of superoxide
dismutase, catalase and deferoxamine to examine the role of superoxide
anions, hydrogen peroxide and hydroxyl radicals. Selective receptor
antagonist and enzymatic pathway inhibitors will be used and the production
of prostanoids will be measured to examine the role of endoperoxides,
prostaglandins and thromboxane A2 in mediating endothelium-dependent
contractions. If superoxide anions or other free radicals cause
contractions, the effects of various substance (oxygen-derived free radical
scavengers and anti-inflammatory drugs) will be examined, to determine
whether they can reduce or prevent endothelium-dependent contraction and
chronic cerebral vasospasm. It is anticipated that those studies will
enhance knowledge of the mechanisms and mediators of cerebral vasospasm and
provide indications for therapies.
StatusFinished
Effective start/end date7/1/906/30/95

ASJC

  • Medicine(all)