A Rabbit Model for Evaluation of Chlorpromazine-Induced Orthostatic Hypotension

元データ 1999-05-15 公益社団法人日本薬学会

概要

The present study was conducted to develop an experimental model for evaluation of chlorpromazine-induced orthostatic hypotension in rabbits. In addition, the α-adrenoceptor blocking effect of chlorpromazine was investigated in isolated rabbit aorta and saphenous vein in comparison with prazosin. Chlorpromazine (0.1 and 1 mg/kg, i.v.) potentiated significantly a decrease in mean blood pressure at 1 min after the onset of head-up tilt in rebbits anesthetized with urethane alone, urethane+α-chloralose or nitrous oxide alone, but not in conscious and morphine+urethane+α-chloralose-anesthetized rabbits. There was a negative correlation (r=-0.986,p<0.01) between the extent of chlorpromazine-induced orthostatic hypotension and the amplitude of tilt-induced reflex tachycardia before chlorpomazine treatment. Both prazosin and pentolinium elicited orthostatic hypotension under all four anesthetic conditions. The pA_2 value for chlorpromazine to antagonize norepinephrine-induced contraction in aorta was significantly larger than that in saphenous vein, whereas prazosin blocked aortic and venous contractions to a similar extent. These results suggest that a rabbit under an anesthesia which impairs tilt-induced reflex tachycardia may be useful for evaluation of orthostatic hypotension by chlorpromazine.The relatively low potential of chlorpromazine to produce orthostatic hypotension may be partly due to its weak venodilating action.

著者

KURIHARA Junichi Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
OKUBO Yoko Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
TAKATA Yoshinobu Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
KATO Hitoshi Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
Kato H Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Takata Yoshinobu Department Of Gastroenterology National Kyushu Cancer Center
Takata Y Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Okubo Y Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Okubo Yoko Department Of Ecological Engineering Toyohashi University Of Technology
Suzuki Shigeto Department Of Civil Engineering Technical College Yamaguchi University
Kato Hitoshi Department Of Pediatrics Kurume University School Of Medicine
Kurihara Junichi Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Kato Hitoshi Department Of Pediatrics Graduate School Of Medicine University Of Tokyo
TAKATA Yoshinobu Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
KATO Hitoshi Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo

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