The presence of the
endothelin isopeptides and
endothelin receptors on neurons, glial cells and brain capillary endothelium suggests that
endothelins may play a significant role in neuromodulation, astrocytic function and in regulation of cerebral blood flow. Furthermore,
endothelins may play a significant role in the central regulation of neuroendocrine and autonomic nervous system functions (i.e., plasma volume, cardiovascular and respiratory control).
Endothelin has potent cerebrovascular and proliferative effects suggesting a pathogenic role in
cerebrovascular diseases.
Endothelin receptors may represent important therapeutic targets for the treatment of both hemorrhagic and
ischemic stroke. A review of the available data on
endothelin levels and the effects of
endothelin antagonists in
cerebrovascular diseases is provided in the present report. Most notably is evidence in support of increased brain
endothelin levels in hemorrhagic and
ischemic stroke both in animal models and in humans. Also,
endothelin receptor antagonists exert significant efficacy in animal models of
cerebrovascular disease. For example,
SB 209670, a rationally designed, potent, nonpeptide
endothelin receptor antagonist, exerts therapeutic efficacy in reducing vasospasm following
subarachnoid hemorrhage and neuroprotection following
ischemic stroke. Certainly the available data warrants further evaluation of novel, selective
endothelin receptor antagonists or
endothelin converting enzyme inhibitors in
cerebrovascular diseases.