Jpn. J. Pharmacol. 83 (2), 135-142 (2000)

Effect of Choto-san, a Kampo Medicine, on the Cerebral Blood Flow
Autoregulation in Spontaneously Hypertensive Rats

Akira Sugimoto^1,#, Kazuhiro Goto^2,*, Atsushi Ishige², Yasuhiro Komatsu² and Ken-ichi Miyamoto<sup>3


1</sup>Departmentﾊof Pharmacology and Pharmaceutics, Division of Pharmacy and Health Sciences, Graduate School of Natural Science
and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
²Kampoﾊand Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Ibaraki 300-1192, Japan
³Departmentﾊof Hospitalpharmacy, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
^#ﾊPresent address: Medical Development DepartmentﾊII, Tsumura & Co., 2 Rokuban-cho, Chiyoda-ku, Tokyo 102-0085, Japan
*ﾊTo whom correspondence should be addressed.

Abstract: To clarify the mechanism of the benefical effect of Choto-san on cerebral circulation in hypertensive patients, the influence of Choto-san on cerebral blood flow (CBF) during hemorrhagic hypotension was evaluated in 10- to 11-month-old spontaneously hypertensive rats. The lower limit of CBF autoregulation, defined as the mean arterial blood pressure at which CBF decreased by 10% of the baseline value, was dose-dependently lowered when Choto-san (0.5-2.0ﾊg/kg per day, p.o.) was administered for 14 consecutive days. Uncariae Ramulus et Uncus (150ﾊmg/kg per day, p.o.), one of the crude drug components of Choto-san, showed an effect equivalent to that of Choto-san. The action of Choto-san (2.0ﾊg/kg per day, p.o.) or Uncariae Ramulus et Uncus on the autoregulatory response of cerebral vessels was eliminated by treatment with N^G-nitro-L-arginine methyl ester (10ﾊmg/kg, i.v.), an inhibitor of nitric oxide synthase. These results suggested that the activation of nitric oxide synthase by Uncariae Ramulus et Uncus contributed to at least part of the improvement in the cerebral circulation caused by Choto-san.

Keywords: Choto-san, Cerebral blood flow autoregulation, Uncariae Ramulus et Uncus, Nitric oxide,
Spontaneously hypertensive rat