Abstract
Numerous studies have addressed the antihypertensive properties of I1-imidazoline receptor agonists such as moxonidine, but very few authors examined their cardiac antiarrhythmic potency. Due to the important role of the sympathetic nervous system in the genesis of neurogenic cardiac arrhythmias, we investigated the antiarrhythmic effects of moxonidine and compared them to those of propranolol in an experimental model of neurogenic arrhythmias. Chronic bipolar electrodes were implanted within the posterior hypothalamus of six halothane-anesthetized rabbits. Every 15 days, after three 10-min-interval control electrical stimulations, we compared the effects of randomized i.v. administrations of moxonidine (25 μg/kg), propranolol (0.5 mg/kg), and saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR), and ECG during 2.5 h with six stimulations every 20 min. We observed that: 1) in control conditions, intrahypothalamic stimulation increased MAP (ΔMAP = 17 ± 2 mm Hg) and HR (ΔHR = 60 ± 1 beats/min), and triggered extrasystoles (number of extrasystoles = 55 ± 2) and abnormal complexes (number of abnormal ECG complexes = 37 ± 1), which occurred with a 6.4 ± 0.4-s delay and 33 ± 1-s duration; 2) moxonidine and propranolol induced almost equihypotensive (ΔMAP = −12 ± 2 and −10 ± 2 mm Hg) and pronounced bradycardic effects (ΔHR = −47 ± 10 and −78 ± 9 beats/min, respectively). Arrhythmias were significantly reduced by moxonidine and propranolol: Δnumber of extrasystoles = −83 and −98%; Δnumber of abnormal ECG complexes = −33 and −79%; Δdelay = +65 and +188%; Δduration = −35 and −58%, respectively. Our results show that moxonidine presents an antiarrhythmic potency comparable to that of propranolol that should be predominantly related to their central action. However, additional studies are required to determine whether these antiarrhythmic effects are of central and/or peripheral origin.
Footnotes
-
Send reprint requests to: Dr. Denise Poisson, Dept. of Neuropharmacology, Faculty of Pharmacy, 31 Ave. Monge, 37200 Tours, France. E-mail:poisson{at}univ-tours.fr
- Abbreviations:
- IR
- imidazoline receptor
- AC
- abnormal ECG complex
- NbAC
- number of abnormal ECG complexes
- BP
- blood pressure
- ES
- extrasystoles
- HR
- heart rate
- IHR
- initial heart rate
- IMAP
- initial mean arterial pressure
- MAP
- mean arterial pressure
- NbES
- number of extrasystoles
- SHR
- maximal heart rate under hypothalamic stimulation
- SMAP
- maximal mean arterial pressure under hypothalamic stimulation
- Received September 22, 1999.
- Accepted February 1, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|