WNK-Cab39-NKCC1 signaling increases the susceptibility to ischemic brain damage in hypertensive rats.

ABSTRACT: With-no-lysine kinase (WNK) and Na⁺-K⁺-2Cl^- cotransporter 1 (NKCC1) are involved in the pathogenesis of hypertension. In this study, we investigated the WNK-NKCC1 signaling pathway in spontaneously hypertensive rats (SHR) and their associated susceptibility to stroke injury. Basal NKCC1 protein levels were higher in SHR than in normotensive Wistar Kyoto (WKY) rat brains. After inducing ischemic stroke, adult male WKY and SHR received either saline or NKCC1 inhibitor bumetanide (10 mg/kg/day, i.p.) starting at 3-h post-reperfusion. NKCC1 inhibition blunted the extent of ischemic infarction in SHR and improved their neurobehavioral functions. Interestingly, ischemia led to increased NKCC1 phosphorylation in SHR but not in WKY rats. Pronounced elevation of WNK

SUBMITTER: Bhuiyan MIH 

PROVIDER: S-EPMC5536788 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature