Abstract 5939: Blockade of a7-Nicotinic Acetylcholine Receptors Attenuates Cardio-protective Effects of Donepezil in Rats With Extensive Myocardial Infarction
Introduction: We have reported that donepezil, an acetylcholinesterase inhibitor has improved long-term survival of rats with chronic heart failure (CHF) after extensive myocardial infarction (MI), but its mechanisms remain unclear. α7-nicotinic acetylcholine receptors (α7-nAChR) reportedly play an important role in inflammation and angiogenesis. We determined the contribution of α7-nAChR by reduction in cardio-protective effects of donepezil in post-MI rats with α7-nAChR blockade.
Methods: Twelve days after extensive (48±3%) myocardial infarction (MI), survived rats (n=31) were implanted an ECG transmitter for monitoring heart rate and arrhythmia. Two days after surgery, all rats were treated with donepezil (5mg/kg/day) and were assigned to group without (DT) or with (α7RBDT) α7-nAChR blocker (methyllyca-conitine, 5μg/kg/day) by osmotic minipumps. At the end of 4-week treatment, the impact of α7-nACR was evaluated by means of hemodynamic parameters, neurohumoral states, and histological examination.
Results: Compared with DT, α7RBDT showed significantly increased heart weight (+10%), deteriorated hemodynamics (cardiac index −49%; dp/dtmax −35%), increased plasma BNP (+42%), norepinephrine (NE, +296%) and cardiac tissue TNF-α (+43%).
Conclusions: α7-nAChR may be one of the important mediators in cholinergic pharmacotherapy for severe CHF.