Involvement of Epithelial Na+ Channel in the Elevated Myogenic Response in Posterior Cerebral Arteries from Spontaneously Hypertensive Rats

Hypertension is characterized by increased peripheral vascular resistance which is related with elevated myogenic response. Recent findings have indicated that epithelial sodium channel (ENaC) is involved in mechanotransduction of the myogenic response. The purpose of this study was to investigate the involvement of ENaC in the elevated myogenic response of posterior cerebral arteries (PCAs) from spontaneously hypertensive rats (SHRs). Sixteen to eighteen weeks old male wistar kyoto rats (WKYs) and SHRs were used in this study. We found that wall to lumen (W/L) ratio was increased in the PCAs from SHRs compared with WKYs at the resting state. Interestingly, amiloride significantly inhibited myogenic response in the PCAs from SHRs and WKYs, however, the magnitude of the blockade was greater in SHRs. The transfection of gamma ENaC-siRNA significantly reduced the expression of gamma ENaC protein and inhibited myogenic response in the PCAs from SHRs. Furthermore, these data were supported by the findings that serum/glucocorticoid-induced kinase (Sgk1) and neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) were increased in SHRs compared with WKYs. Our results suggest that gamma ENaC may play an important role in the elevated myogenic response in PCAs from SHRs.