title: Protective effects of angiotensin II type 1 receptor blocker on cerebral circulation independent of blood pressure.
abstract: Angiotensin II type 1 receptor (AT1R) blocker (ARB) has been reported to modify hypertensive cerebrovascular changes; however, it is not clear whether its protective effects are independent of blood pressure. The aim of this study was to clarify the role of AT1R-mediated signals in cerebral circulation by the chronic treatment with telmisartan, an ARB, at a dose that did not lower the blood pressure. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were treated for 4 weeks from 16 weeks of ages with telmisartan (SHR-L: 0.3 mg/kg/day, SHR-H: 3 mg/kg/day, WKY-H: 3 mg/kg/day) or vehicle (SHR-V, WKY-V). Superoxide measured by a chemiluminescent assay or dihydroethidium fluorescence and vascular morphology were examined for the thoracic aorta (Ao), common carotid (CCA), middle cerebral (MCA) and basilar arteries (BA). After 4 weeks of treatment, the blood pressure significantly declined in SHR-H but not in SHR-L in comparison to SHR-V. The lower limit of cerebral blood flow (CBF) autoregulation, evaluated by hemorrhagic hypotension, was significantly lower in SHR-L and SHR-H than SHR-V. In both SHR and WKY, the superoxide levels in the arteries were significantly attenuated by both doses of ARB. ARB also reversed vascular hypertrophy in Ao, CCA and BA and the inward remodeling in MCA. These results suggest that chronic treatment with telmisartan may therefore improve CBF autoregulation with a restoration of the vascular structure and an attenuation of superoxide generation, even at a dose that does not lower the blood pressure.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kumai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ooboshi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ago
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Takada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamouchi
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.forename: Setsuro
authors.initials: S
authors.lastname: Ibayashi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iida
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001488:Basilar Artery / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D017536:Carotid Artery, Common / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D000077333:Telmisartan; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D013481:Superoxides; D000077333:Telmisartan