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

Manipulation of the central endothelin (ET) system via either ET A antagonists or ET B 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 (K d ) and density (B max ) of ET A and ET B 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). B max increased (P d decrease d (P A receptors in the infarcted right cerebral hemisphere compared to sham 24 h post MCAO. However, after 7 days of MCAO, B max of ET A receptors was similar, while K d in the infarcted hemisphere increased (P B receptors were not altered 24 h post MCAO. However, 7days following MCAO, there was a significant decrease (P d values and an increase (P max values for ET B receptors in the ischemic cerebral hemisphere. The initial increase in ET A receptors is damaging and may be aggravating cerebral ischemia due to its vasoconstrictive actions. On the other hand, since ET B 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.