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

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ABSTRACT

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 γENaC-siRNA significantly reduced the expression of γENaC 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 γENaC may play an important role in the elevated myogenic response in PCAs from SHRs.

No MeSH data available.


Related in: MedlinePlus

Expression of Sgk1 and phosphorylation of Nedd4-2 in the PCAs from SHRs and WKYs.The gels were run under the same experimental conditions while images of blots displayed in cropped format. (A) Western blots showing the expression level of Sgk1. (B) Western blots showing the phosphorylation level of Nedd4-2. p < 0.05 for WKYs vs. SHRs. Data are expressed 100% in WKYs. (n = 4 in Sgk1 and n = 6 in phospho-Nedd4-2).
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f5: Expression of Sgk1 and phosphorylation of Nedd4-2 in the PCAs from SHRs and WKYs.The gels were run under the same experimental conditions while images of blots displayed in cropped format. (A) Western blots showing the expression level of Sgk1. (B) Western blots showing the phosphorylation level of Nedd4-2. p < 0.05 for WKYs vs. SHRs. Data are expressed 100% in WKYs. (n = 4 in Sgk1 and n = 6 in phospho-Nedd4-2).

Mentions: To test whether the up-stream signaling molecules of ENaC change in the SHRs, we observed the expression of Sgk1 and phosphorylation of Nedd4-2 in the PCAs from WKYs and SHRs. As shown in the Fig. 5, expression level of Sgk1 was increased in the PCAs from SHR compared with those from WKY. Moreover, phosphorylation level of Nedd4-2 was also significantly increased in the PCAs from SHR compared with those from WKY.


Involvement of Epithelial Na + Channel in the Elevated Myogenic Response in Posterior Cerebral Arteries from Spontaneously Hypertensive Rats
Expression of Sgk1 and phosphorylation of Nedd4-2 in the PCAs from SHRs and WKYs.The gels were run under the same experimental conditions while images of blots displayed in cropped format. (A) Western blots showing the expression level of Sgk1. (B) Western blots showing the phosphorylation level of Nedd4-2. p < 0.05 for WKYs vs. SHRs. Data are expressed 100% in WKYs. (n = 4 in Sgk1 and n = 6 in phospho-Nedd4-2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382693&req=5

f5: Expression of Sgk1 and phosphorylation of Nedd4-2 in the PCAs from SHRs and WKYs.The gels were run under the same experimental conditions while images of blots displayed in cropped format. (A) Western blots showing the expression level of Sgk1. (B) Western blots showing the phosphorylation level of Nedd4-2. p < 0.05 for WKYs vs. SHRs. Data are expressed 100% in WKYs. (n = 4 in Sgk1 and n = 6 in phospho-Nedd4-2).
Mentions: To test whether the up-stream signaling molecules of ENaC change in the SHRs, we observed the expression of Sgk1 and phosphorylation of Nedd4-2 in the PCAs from WKYs and SHRs. As shown in the Fig. 5, expression level of Sgk1 was increased in the PCAs from SHR compared with those from WKY. Moreover, phosphorylation level of Nedd4-2 was also significantly increased in the PCAs from SHR compared with those from WKY.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus