Acute, servere increases in arterial blood pressure cause sustained cerebral arteriolar dilation, abnormal reactivity to carbon dioxide and to changes in blood pressure, abolition of the endothelium dependent dilation from acetylcholine,
discreate
morphological lesions of the endothelium and vascular smooth muscle, and breakdown of the blood-brain barrier to plasma proteins. The dilation, abnormal reactivity, and morphological abnormalities are inhibited by tase-inhibitable reduction of
nitroblue
tetrazolium applied to the brain surface was detectable both during hypertension an done hour after hypertension subsided.
Nitroblue tetrazolium reduction is also reduced by topical application of arachidonate. The results are consistent with the view that acute hypertension induces generation of suporoxide anion radical in association with accelerated arachidonate
metabolism via cyclooxygenase.
This radical enters cerebral extracellular space via the anion channel and gives rise to hydrogen peroxide and hydroxyl radical. All three radicals are capable of causing vasodilation by relaxation of cerebral vascular smooth muscle. The hydroxyl
radical is the most likely candidate for vascular wall damage. The significance of this mechanism in chronic experimental hypertension or its relevance to human disease is not known.
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