title: Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats.
abstract: 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.
authors.affiliation: Dept of Pharmacology, College of Medicine, Univ of Arizona, Tucson, AZ 85724, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hom
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Fleegal
authors.forename: Richard D
authors.initials: RD
authors.lastname: Egleton
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Campos
authors.forename: Brian T
authors.initials: BT
authors.lastname: Hawkins
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
mesh_terms: D000375:Aging; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism
chemical_list: D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1