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 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 mm³ on days 1 and 7, respectively). B_max increased (P<0.01) and K_d decrease_d (P<0.01) for ET_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<0.05) compared to sham. Binding characteristics for brain ET_B receptors were not altered 24 h post MCAO. However, 7days following MCAO, there was a significant decrease (P<0.001) in K_d values and an increase (P<0.001) in B_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.

Key words

cerebral ischemia - endothelin - receptor binding - ET_A receptors - ET_B receptors

• References

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