Chronic administration of moxonidine suppresses sympathetic activation in a rat heart failure model

Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts

“…The tachycardic effect of captopril is in accordance with previous functional observations in early captopril treated rats, and could probably be attributed to compensation of a reduced stroke volume in order to maintain cardiac output [12]. With regard to moxonidine, a clear relation between sympathetic suppression and reduced in vivo heart rate has been previously demonstrated in experimental [11] and clinical studies [28,29]. However, the reduction of the in vivo tachycardia by aspirin and methylprednisolone treatment cannot as easily be explained by reduced sympathetic activity, which is further supported by unchanged plasma catecholamine concentrations in aspirin [14] and methylprednisolone treated rats (data not shown).…”

“…During the first 3 weeks post MI, four types of therapy were examined in coronary artery ligated rats [10], with regard to effects on heart rate, left ventricular hypertrophy and capillary density. Captopril and moxonidine both are anticipated to inhibit the hypertrophic response, but with opposite effects on heart rate [11,12]. Methylprednisolon and aspirin did not inhibit heart weight body weight ratio [13], while aspirin is previously reported to reduce heart rate [14].…”

“…The centrally acting sympatholytic moxonidine (Solvay Pharma, Hannover, Germany) was dissolved in acidified saline to provide a final daily dose of 6 mg/kg/day using subcutaneously implanted osmotic minipumps (AlzetR 2001, ALZA Pharmaceuticals, Palo Alto, CA, USA) [11]. Administration of moxonidine was started 24 h following MI and continued until the end of the experiment at 21 days after surgery.…”

Feedback Inhibition of Catecholamine Release by Two Different α 2 -Adrenoceptor Subtypes Prevents Progression of Heart Failure

“…32 Activation of central ␣ 2 -adrenoceptors by clonidine or moxonidine suppressed the sympathetic nervous system in congestive heart failure. [7][8][9] However, moxonidine had serious adverse effects and was even associated with increased lethality of patients. 8,9 Our data from gene-targeted mice suggest that subtype-specific activation of ␣ 2 -receptor subtype may be advantageous over nonselective ␣ 2 -receptor stimulation to prevent serious side effects of ␣ 2 -agonists.…”

“…4 -6 In addition to inhibition of myocardial ␤-adrenoceptors, activation of ␣ 2 -adrenoceptors has recently been investigated as a therapeutic strategy in experimental and in clinical studies of heart failure. [7][8][9] …”