Jpn. J. Pharmacol. 85 (2), 197-202 (2001)

Disturbance of Circadian Rhythm in Heart Rate, Blood Pressure and Locomotive Activity at the Stroke-Onset in Malignant Stroke-Prone Spontaneously Hypertensive Rats

Masaki Tabuchi1, Keizo Umegaki2, Tomohiro Ito1, Motohisa Suzuki1, Masahiko Ikeda1 and Takako Tomita1,*

1Graduate School of Health Sciences, University of Shizuoka, 52-1, Yada, Shizuoka-shi, Shizuoka 422-8526, Japan
2Division of Applied Food Research, The National Institute of Health and Nutrition, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8636, Japan
*Corresponding author. FAX: +81-54-264-5787

Abstract: Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP), separated from SHRSP, develop severe hypertension and spontaneously develop stroke at early ages. Using this model of cerebrovascular stroke, influence of stroke-onset on the autonomic nervous system was investigated. Heart rate (HR), systolic and diastolic blood pressures (SBP and DBP) and locomotive activity were monitored during development of stroke using a telemetry system. Stroke-onset was assessed by neurologic symptoms, changes in body weight, fluid intake and serum NOx level. The rat displayed a nocturnal pattern of circadian rhythms. At stroke-onset, mean HR over 24 h increased by 20 to 30 bpm and rapidly increased at post stroke, approximately 100 bpm higher than that at pre stroke. Circadian variation in HR, which was normally 50 bpm higher during night than during day, attenuated at stroke-onset, and it was blunted or reversed at post stroke. BP variation, which was approximately 7 mmHg higher at night than at day, decreased one or two days before stroke-onset and reversed at post stroke, especially in DBP. Insufficient falls in HR and BP during the day mainly accounted for the disturbed circadian variations. Variation of locomotive activity also decreased. These changes serve as reliable and accurate markers for stroke-onset in evaluation of drugs for the prevention and outcome predictions of stroke.

Keywords: Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP), Stroke, Circadian rhythm, Heart rate, Blood pressure

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