Jpn. J. Pharmacol. 83 (1), 39-45 (2000)

New Approach for Measurement of Sympathetic Nervous Abnormality in Conscious, Spontaneously Hypertensive Rats

Makoto Tsunoda1, Kazuko Takezawa1, Tomofumi Santa1, Yasuhiro Ina2, Ken Nagashima2, Kenji Ohmori2, Satoshi Kobayashi2 and Kazuhiro Imai1,*

1Department╩of Bio-Analytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo,
7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2Drug╩Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.,
1188, Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan
*To whom correspondence should be addressed.

Abstract: We previously reported a highly sensitive chemiluminescence high-performance liquid chromatographic method to determine catecholamines in plasma. In this study, we employed this method to measure the cardiac function and plasma norepinephrine (NE) concentration in conscious rats. Benidipine, 1,4-dihydropyridine calcium antagonist (4 mg/kg), and b-blocker (propranolol, 30 mg/kg) were administered orally to conscious spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats, and blood pressure, heart rate and plasma NE levels were measured. Plasma NE concentration was used as an index of sympathetic nervous system activity in conscious rats. The basal plasma NE levels were significantly higher in SHRs than in WKY rats (P<0.05), indicating the activity of the basal sympathetic nervous system in SHRs was elevated. The sensitivity of the baroreflex-mediated sympathetic nervous response was reduced in SHRs as compared to that in WKY rats. The concomitant administration of benidipine and a b-blocker decreased heart rate without affecting the baroreflex-mediated sympathetic nervous response, indicating that propranolol might suppress mainly the cardiac b-adrenoceptor. The present study suggested the high activity of the basal sympathetic nervous system and the reduced response of the baroreflex-mediated sympathetic nervous system in SHRs compared to WKY rats in the conscious condition.

Keywords: Benidipine, Plasma norepinephrine, Blood pressure, Tachycardia, Conscious rat

Copyrightę The Japanese Pharmacological Society 2000

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