Aims: 

Moxonidine is successfully used to reduce blood pressure (BP) in essential hypertension. However, its administration to heart failure patients was associated with increased mortality. Hypothesis was tested that a parasympatholytic effect could be responsible for this unexpected outcome of the MOXCON trial.

Methods: 

Wistar male rats (8) were implanted with telemetric transmitters to monitor BP, ECG, temperature and animal activity. Moxonidine (40, 120, 360, 1080 mg/kg) was applied s.c. in four successive days. Cardiovascular and respiratory oscillations were analysed.

Results: 

Low dose moxonidine (120 mg/kg) reduces overall intensity of the autonomic modulation of the cardiovascular system (-59% total variance (TV) of heart rate (HR), p < 0.05; -66% TV of mean BP, p < 0.05). Sympathetic system was affected more (-62% low frequency variance (FV) of diastolic BP, p < 0.05) than the parasympathetic system (-15% cardiac vagal index, p < 0.05). High dose (1080 mg/kg) attenuated the total BP variance (-56%, p < 0.05) but augmented total HR variance (+41%, p < 0.05). Sympathetic activity was diminished stronger than with the low dose (-85% low FV of diastolic BP, p < 0.05), however the parasympathetic modulation was intensified (+170% RMSSD of HR, p < 0.05). Baroreflex sensitivity was increased as well (1.12ms/mmHg control vs. 2.37ms/mmHg after high dose moxonidine, p < 0.05). A dose dependent reduction in the respiratory frequency was also registered (-17% after high dose, p < 0.05).

Conclusion: 

Lower doses of moxonidine seem to have parasympatholytic effects while higher doses are parasympathomimetic. Depression of respiration might be related to the negative impact of moxonidine in the heart failure patients. Activation of different receptors, i.e. imidazoline and alpha2-adrenergic receptors could be responsible for these dose dependent differences in moxonidine effects.

Supported: Kuwait University grant MY02/04.