Abstract
Increased levels of endothelin-1 have been demonstrated in the ischemic brain, and endothelin receptor antagonism has been shown to improve the outcome of cerebral ischemia. However, it remains unknown what the relative receptor distribution in the brain of the spontaneously hypertensive stroke-prone rat (SHR-SP) is and whether it is changed by endothelin antagonism. The present study aimed to investigate the expression of the two endothelin receptors in the frontal cortex of SHR-SP after 12 weeks of treatment with an endothelin-A/endothelin-B dual receptor antagonist, SB209670, or saline (vehicle) starting from the prehypertensive stage (6 weeks old). A 50% increase in the endothelin-A receptor was found in the vehicle-treated brain of SHR-SP compared with that of the age-matched Wistar-Kyoto control, but endothelin antagonism reversed this upregulation completely. A 20% decrease in endothelin-B receptor was found in the vehicle-treated brain of SHR-SP compared with Wistar-Kyoto and was recovered by endothelin antagonism. This is the first study to explore the relative endothelin receptor distribution in the frontal cortex of SHR-SP at the typical hypertensive stage and changes resulting from long-term endothelin antagonism starting from the prehypertensive stage.
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