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 Imai^{1,*

¹Departmentﾊof Bio-Analytical Chemistry, Graduate School of
Pharmaceutical Sciences, The University of Tokyo,

7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

²Drugﾊ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}