Antihypertensive effects, determined by a telemetry method, of trichloromethiazide and 7-O-ethylfangchinoline, a derivative of tetrandrine, in spontaneously hypertensive rats.
1. The antihypertensive effects of 10 mg/kg trichloromethiazide (TCM), 10 mg/kg 7-O-ethylfangchinoline (7-O-EFC) and the combination of these drugs given orally once daily for 2 weeks were investigated by measuring the blood pressure (BP), heart rate (HR) and activity in conscious, freely moving spontaneously hypertensive rats (SHR) fitted with a telemetry device. 2. Clear diurnal rhythms of the HR and activity in synchrony with the light/dark cycle were observed during therapy, whereas the BP rhythm was obscure. 3. Alone, TCM and 7-O-EFC produced slight and insignificant reductions of 24h mean BP, whereas in combination they produced an additive and significant BP reduction, compared with the vehicle-treated controls, from the third day of therapy. The BP reduction induced by the combination of these drugs during the dark phase was more marked than that during the light phase. 4. None of the drug therapies affected the HR and activity diurnal rhythms. 5. The results of the present study demonstrate that the telemetry method is useful for monitoring the antihypertensive effects of drugs in SHR under physiological conditions with minimal stress.
Kawashima
K
K
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Negishi
T
T
Amano
H
H
Fujimoto
K
K
Suzuki
T
T
Fujii
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry; D014237:Trichlormethiazide / Q000494:pharmacology*
D000470:Alkaloids; D000959:Antihypertensive Agents; D044182:Benzylisoquinolines; C069407:7-O-ethyl fangchinoline; C009438:tetrandrine; D014237:Trichlormethiazide