Distinct Alteration in Brain Endothelin A and B Receptor Characteristics Following Focal Cerebral Ischemia in Rats.

Abstract

Manipulation of the central endothelin (ET) system via either ETA antagonists or ETB agonists following experimental cerebral ischemia has been shown to be beneficial in previous experimental studies. In order to further explore the involvement of these receptors in cerebral ischemia, we determined changes in binding affinity (Kd) and density (Bmax) of ETA and ETB receptors in the rat brain at 24 h and 1 week following middle cerebral artery occlusion (MCAO). Rats subject to MCAO exhibited significant neurological and motor function deficit as well as large infarct volumes (126.41±40.12 and 152.82±21.67 mm(3) on days 1 and 7, respectively). Bmax increased (P<0.01) and Kd decreased (P<0.01) for ETA receptors in the infarcted right cerebral hemisphere compared to sham 24 h post MCAO. However, after 7 days of MCAO, Bmax of ETA receptors was similar, while Kd in the infarcted hemisphere increased (P<0.05) compared to sham. Binding characteristics for brain ETB receptors were not altered 24 h post MCAO. However, 7days following MCAO, there was a significant decrease (P<0.001) in Kd values and an increase (P<0.001) in Bmax values for ETB receptors in the ischemic cerebral hemisphere. The initial increase in ETA receptors is damaging and may be aggravating cerebral ischemia due to its vasoconstrictive actions. On the other hand, since ETB receptors have been shown to enhance brain angiogenesis, it is possible that an increase in binding characteristics of these receptors is part of a natural defense mechanism to repair the ischemic brain.