Autoradiographic study of endothelin receptors in human cerebral arteries

Endothelin (ET) has recently been implicated in the pathogenesis of a variety of cerebrovascular disorders. In particular, it has been linked to the delayed cerebral vasospasm associated with subarachnoid hemorrhage (SAH). In the present study we have identified the ET receptors present on human middle meningeal and pial arteries. Qualitative autoradiography was carried out using [125I]ET-1 to visualize the total ET receptor population or [125I]PD151242, or [125I]BQ3020, ETA- and ETB-selective receptor ligands, respectively. [125I]ET-1 and [125I]PD151242 bound specifically with high density to the vascular smooth muscle of both arteries; little or no specific [125I]BQ3020 binding was detected. Immunocytochemistry localized the mature ET to endothelial cells of pial arteries. These results show that ETA receptors predominate in human middle meningeal and pial arteries. In pial arteries, ET, which may be synthesized locally by the endothelium, may then act on this receptor subtype. However, it has yet to be determined whether this receptor subtype is involved in conditions such as the delayed vasospasm associated with SAH. The possibility of changes in ET receptor subtype(s) under pathophysiologic conditions should be considered.