Effects of moxonidine versus clonidine on arterial pressure and heart rate in renal-hypertensive rats

Wei ZHANG; Yuqin WANG; Weizhong ZHU

ABSTRACT

BACKGROUND:

Moxonidine is the second-generation high-selective central antihypertensive drug, while clonidine is the first-generation antihypertensive drug that is used in clinic with many side effects.

OBJECTIVE:

To compare the characteristics between moxonidine and clonidine in renal-hypertensive rats.

DESIGN:

Randomized controlled animal experiment.

SETTING:

Department of Pharmacology, Medical College, Nantong University.MATERIALS The experiment was conducted in Medical College, Nantong University between September and December 2004. Totally 110 SD rats aged 60 days with the body mass of (180±30) g were used in the study.

METHODS:

Left renal artery stenosis in SD rats was established by inserting silver clip with the inner diameter of 0.2 mm or 0.25 mm, while the right renal artery was not received, so as to establish two-kidney one-clip(2K-1C) renal hypertensive models. ①Changes of blood pressure and heart rate in awake rats with renal hypertension were determined with arteria caudilis indirect manometric method, oral administration once or consecutively. The experiment of depressurization with once oral administrationThe rats were randomly assigned into 5 groups with 10 rats in each group1 mg/kg, 3 mg/kg, 10 mg/kg moxonidine hydrochloride groups, 1 mg/kg clonidine hydrochloride group were considered as positive control group,while saline group as negative control group. On the basis of the effect of moxonidine hydrochloride on blood pressure, blood pressure was measured at 1, 4, 24, 48, 72 hours after moxonidine administration, and compared with that before administration or the effect of saline. The experiment of depressurization with consecutively oral administration once a day. The grouping was the same to above-mentioned. Successive administration was for 7 days, once a day. The blood pressure and heart rate were determined at 1 hour before and after administration, and observed for 3 days after drug withdrawal. Recommended dose of moxonidine hydrochloride for human was about 0.4 mg/kg, while the oral dose for rats were around 0.04 mg/kg based on the animals' surface area. ②Changes of blood pressure and heart rate in anaesthesia rats with renal hypertension with a catheter on the carotid artery directly 0.2 mg/kg drug liquor was given with gastric perfusion. The rats were randomly divided into 5 groups with 10 ones in each group 0.13,0.4, 1.3 mg/kg moxonidine hydrochloride groups, 0.13 mg/kg clonidine hydrochloride group and saline control group. Mean arterial pressure was determined before and after administration at different time.MAIN OUTCOME

MEASURES:

Changes of blood pressure and heart rate in conscious and anesthetized renal-hypertensive rats before and after being administrated orally once or consecutively.

RESULTS:

All the rats were involved in the result analysis, without drop out during the trial. ①Moxonidine showed a dose-dependent effect on depressurization and descent of heart rate after once large dose oral administration in conscious renal-hypertensive rats. The 10-fold higher doses of moxonidine caused the same effects of clonidine. The decreasing of heart rate was little and short after consecutively small dose of oral administration of moxonidine, and which was similar to clonidine in percentage of depressurization. ②In anesthetized renal-hypertensive rats, moxonidine showed a dose-dependent effect on depressurization after once oral administration. There was no significant difference between moxonidine and clonidine in percentage of depressurization after 3 to 10-fold higher dose administration (P ＞ 0.05).

CONCLUSION:

The once higher dose oral administration of moxonidine has dose-dependent effect on depressurization for renal-hypertensive awake rats. Anesthesia. The effect of 10-fold dosage of moxonidine is equal to that of clonidine. The effect of 3-10-fold dosage of moxonidine is equal to that of clonidine in anesthesia renal-hypertensive rats. The small dose oral administration continuously of both moxonidine and clonidine with the same volume has the same depressurization effect in renal-hypertensive rats.