In the present study we investigated the chronopharmacological dependence of dose-dependent hypotensive and cardiochronotropic effects of the imidazoline-like drugs (clonidine, rilmenidine and moxonidine) in stroke-prone spontaneously hypertensive rats (SHR-SP), using radio-telemetric system (Data Sciences, USA). The 24-h blood pressure, heart rate and locomotor activity profiles showed peak values during the rats' active phase during the night period. The degree of hypotensive and bradycardic effects of all drugs were most evident at this time and occurred in the absence of a change in locomotor activity. These studies show that clonidine, rilmenidine and moxonidine decrease blood pressure and heart rate in a time-dependent manner in SHR-SP. It was demonstrated that the degree and duration of hypotensive action of imidazoline-like drugs vary with the time of drug administration.

Chronopharmacological dependence of antihypertensive effects of the imidazoline-like drugs in stroke-prone 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.

Antihypertensive effects, determined by a telemetry method, of trichloromethiazide and 7–o‐ethylfangchinoline, a derivative of tetrandrine, in spontaneously hypertensive rats

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Antihypertensive effects, determined by a telemetry method, of trichloromethiazide and 7–o‐ethylfangchinoline, a derivative of tetrandrine, in spontaneously hypertensive rats