Effects of Benidipine, a Long-Lasting Dihydropyridine-Ca super(2+) Channel Blocker, on Cerebral Blood Flow Autoregulation in Spontaneously Hypertensive Rats

• Published in: Biological & pharmaceutical bulletin Vol. 29; no. 11; pp. 2222 - 2225
• Main Authors: Ikeda, J-I, Yao, K, Matsubara, M
• Format: Journal Article
• Language: English
• Published: 01.11.2006
• ISSN: 0918-6158

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 flowme-try 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 (3 mg/kg) for 8 d lowered the mean arterial blood pressure and cerebral vascular resistance, which were equivalent to the effects of amlodipine (3 mg/kg), another CCB, or candesartan (1 mg/kg), an Angiotensin II type-1 receptor blocker. The lower limit of CBF autoregulation in SHRs (142 plus or minus 4mmHg) was significantly shifted to a higher-pressure level compared with Wistar rats (59 plus or minus 2 mmHg). The lower limit of CBF autoregulation was significantly lower in the benidipine-treated group (91 plus or minus 4 mmHg) than that in the control SHRs, and similar to that of the amlodipine group (97 plus or minus 6 mmHg). Benidipine reduced the lower limit of CBF autoregulation more effectively than candesartan (109 plus or minus 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 cere-brovascular disorders, in whom autoregulation of CBF is impaired.