Hypertension is involved in the exacerbation of
stroke. It is unclear how blood-brain barrier (BBB) tight-junction (TJ) and ion transporter
proteins critical for maintaining brain homeostasis contribute to
cerebral infarction during
hypertension development. In the present study, we investigated
cerebral infarct volume following permanent 4-h
middle cerebral artery occlusion (MCAO) and characterized the expression of BBB TJ and ion transporter
proteins in brain microvessels of spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) rats at 5 wk (
prehypertension), 10 wk (early-stage
hypertension), and 15 wk (later-stage
hypertension) of age. Hypertensive SHR show increased
infarct volume following MCAO compared with WKY control rats. BBB TJ and ion transporter
proteins, known to contribute to
edema and fluid volume changes in the brain, show differential
protein expression patterns during
hypertension development. Western blot analysis of TJ
protein zonula occludens-2 (ZO-2) showed decreased expression, while ion transporter,
Na(+)/H(+) exchanger 1 (NHE-1), was markedly increased in hypertensive SHR. Expression of TJ
proteins ZO-1,
occludin, actin,
claudin-5, and Na(+)-K(+)-2Cl(-) cotransporter remain unaffected in SHR compared with control. Selective inhibition of NHE-1 using
dimethylamiloride significantly attenuated
ischemia-induced
infarct volume in hypertensive SHR following MCAO, suggesting a novel role for NHE-1 in the brain in the regulation of
ischemia-induced
infarct volume in SHR.