Selective inhibition of endothelin receptor A improves white matter lesions in hypertensive rats

AIM:To observe whether selective inhibition of endothelin receptor A (ETRA) improves white matter lesions (WMLs), and explore the mechanism. METHODS:Sprague-Dawley rats (n=33) were randomly divided into sham operation group (n=9), treatment groupstroke-prone renovascular hypertensive rats-modified 2 vessel occlusion (RHRSP-modified 2VO) + ambrisentan (n=12)] and placebo groupRHRSP-modified 2VO + vehicle (n=12)]. Drug and vehicle administration was performed from 17th to 20th week and monitoring of systolic arterial pressure was performed weekly. Morris water maze test was conducted to evaluate the function of cognition. The protein levels of endothelin-1 (ET-1) in the cortex, corpus callosum and caudate putamen were quantitatively analyzed respectively. The severity of WMLs and the relationship between ET-1 and vessels were observed by the method of histopathology. RESULTS:The difference of systolic arterial pressure between treatment group and placebo group was not significant. The animals in treatment group exhibited shorter escape latency (P<0.05), more times of crossing platform (P<0.05), lower level of ET-1 in corpus callosum and caudate putamen (P<0.05), respectively, improved WMLs severity (P<0.05) and lower binding level of ET-1 to vessels compared with the placebo group. CONCLUSION:Selective inhibition of endothelin receptor A improves the severity of WMLs and ameliorates the cognitive function.