Effects of Benidipine, a Long-Lasting Dihydropyridine-Ca^<2+> Channel Blocker, on Cerebral Blood Flow Autoregulation in Spontaneously Hypertensive Rats(Pharmacology)
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概要
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Chronic hypertension shifts cerebral blood flow (CBF) autoregulation towards higher blood pressure. We examined whether or not benidipine, a long-lasting dihydropyridine calcium channel blocker (CCB), improves the CBF autoregulation in spontaneously hypertensive rats (SHRs). CBF was analyzed by laser-Doppler flowmetry during stepwise hypotension by controlled bleeding. The lower limit of CBF autoregulation was calculated as the mean arterial blood pressure at which CBF decreased by 10% of the baseline. Mean arterial blood pressure and cerebral vascular resistance in SHRs were higher than those in normotensive Wistar rats. Oral administration of benidipine (3mg/kg) for 8d lowered the mean arterial blood pressure and cerebral vascular resistance, which were equivalent to the effects of amlodipine (3mg/kg), another CCB, or candesartan (1mg/kg), an Angiotensin II type-1 receptor blocker. The lower limit of CBF autoregulation in SHRs (142±4mmHg) was significantly shifted to a higher-pressure level compared with Wistar rats (59±2mmHg). The lower limit of CBF autoregulation was significantly lower in the benidipine-treated group (91±4mmHg) than that in the control SHRs, and similar to that of the amlodipine group (97±6mmHg). Benidipine reduced the lower limit of CBF autoregulation more effectively than candesartan (109±4mmHg). In conclusion, benidipine shifted the limit of CBF autoregulation towards lower blood pressure in SHRs under hypotensive conditions by hemorrhage. These results suggest that benidipine may be useful for the treatment of hypertensive patients with the elderly or cerebrovascular disorders, in whom autoregulation of CBF is impaired.
- 2006-11-01
著者
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Ikeda Jun-ichi
Department Of Pharmacology And Molecular Biology Pharmaceutical Research Center Kyowa Hakko Kogyo Co
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Ikeda Jun-ichi
Department Of Neurosurgery Kumamoto University Medical School
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Yao Kozo
Department Of Pharmacology And Molecular Biology Pharmaceutical Research Center Kyowa Hakko Kogyo Co
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Matsubara Masahiro
Department Of Pharmacology And Molecular Biology Pharmaceutical Research Center Kyowa Hakko Kogyo Co
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Matsubara Masahiro
Department Of Electronics Faculty Of Engineering Kyoto University
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Yao Kozo
Department Of Pharmacology And Molecular Biology Pharmaceutical Research Center Kyowa Hakko Kogyo Co
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