Search

Kardos, a preparation containing ultralow doses of antibodies to C-terminal fragment of type 1 receptor of angiotensin II, intragastrically administered to SHR rats with hereditary hypertension for 28 days reduced blood pressure by 14.8%. Kardos was not inferior to losartan and, in contrast to the latter reduced HR by 9.4%.

Long-term peroral administration of the oxatriazolo-5-olate derivative azasydnon-6 leads to a decrease in the systolic arterial blood pressure in SHR rats. The hypotensive effect of azasydnon-6 is mediated by stimulation of the sGC-cGMP pathway, which triggers vasodilatation of SMC in vessels. The drug effect is inhibited by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one, a selective sGC inhibitor. During long-term treatment, no tolerance to azasydnon-6 is developed in isolated arterial vessels.

Intravenous administration of azasidnon-6 (oxatriazolium-5-olate derivative) induces prolonged dose-dependent decrease in arterial blood pressure in awake Wistar and SHR rats. Hypotensive effects of azasidnon-6 in SHR rats is significantly higher during inhibition of endogenous NO synthesis.

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.

Earlier findings have shown that hypotensive effects of centrally acting drugs, such as clonidine, are enhanced in animals after denervation of arterial baroreceptors. The purpose of this study was to investigate the dynamic of changes in arterial pressure, heart rate and hypotensive effects of clonidine, rilmenidine and moxonidine in Wistar rats after sino-aortic denervation (SAD) using radio-telemetry. SAD was followed by significant elevation of arterial pressure lability (the standard deviation of the mean arterial pressure), while the baseline mean arterial pressure (MAP) and heart rate in barodenervated rats (12 days after SAD) was similar to intact rats. The hypotension produced by clonidine, rilmenidine and moxonidine was much greater in SAD rats than in intact rats. The study suggests that baroreflex mechanisms are not only important for maintaining levels of blood pressure in the very short term, but also for buffering the effects of centrally acting antihypertensive drugs.

Changes in hemodynamic parameters in intravenous infusion of drugs of the clonidine group were studied in Wistar rats by means of the radio-telemetry and catheter systems of arterial pressure (AP) recording. Clonidine (5 micrograms/kg), rilmenidine (300 micrograms/kg), and moxonidine (100 micrograms/kg) were found to cause significant decrease in AD and bradycardia whatever the method of AD measurement used. However, the degree of the hypotensive and negative cardiochronotropic effects of the central action drugs was higher in rats with radio-telemetry transmitters. The results provide evidence that the radio-telemetry system of monitoring of the hemodynamic parameters is more sensitive and accurate for evaluating the effect of the drugs under study.

Radiotelemetric monitoring of hemodynamic parameters was conducted in Wistar rats to study the chronobiological dependence of the effect of clonidine on changes in arterial pressure (AP) and heart rate (HR) induced by immobilization stress. Clonidine injection (20 mg/kg intraperitoneally) caused significant decrease in AD at night both at rest and under stress, whereas at day time its hypotensive effect was manifested only in case of immobilization. The negative cardiochronotropic effect of clonidine was also time-dependent. Thus, chronobiological dependence of the clonidine effects at rest and under stress was disclosed.