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- W2780059547 abstract "Introduction: Parasympathetic activation by donepezil, a cholinesterase inhibitor, improves prognosis in chronic heart failure (CHF) rats, but its mechanisms remain unclear. a7-nicotinic acetylcholine receptors (a7-nAChR) reportedly play an important role in inflammation and angiogenesis. This study examined if blockade of a7-nAChR either centrally or peripherally cancels the beneficial effect of donepezil on CHF rats. Methods: One week after extensive (48±4%) myocardial infarction (MI), survived rats were implanted with an ECG transmitter for monitoring heart rate. Seven days after surgery, these MI rats (n=57) were all treated with donepezil (5 mg/kg/day) and were randomly assigned to the following 4 groups: central (a7BDT) or peripheral (a7PDT) infusion of a7-nAChR blocker (methyllcaconitine), and central (SBDT) or peripheral (SPDT) infusion of vehicle. After 4 weeks treatment, the role of a7-nACR was evaluated by means of hemodynamic parameters, neurohumoral states, and histological examination. Results: In central infusion groups, a7BDT (vs. SBDT) showed no changes in either cardiac remodeling (2.90±0.19 vs. 2.87±0.18 g/kg) or hemodynamics (cardiac index 111±28 vs. 111±31 ml/min/kg; LVEDP 25±13 vs. 28±7 mmHg; dp/dtmax 3811±579 vs. 3981±647 mmHg/s). In contrast, in peripheral infusion groups, a7PDT (vs. SPDT) had significantly higher heart weight and cardiac fibrosis (3.02±0.28 vs. 2.74±0.24 g/kg, p Conclusions: Peripheral blockade of a7-nAChR significantly erases the cardio-protective effects of donepezil in CHF rats, while central blockade does not; suggesting peripheral activation of a7-nAChR plays an important role in cholinergic pharmacotherapy for severe CHF with extensive MI." @default.
- W2780059547 created "2018-01-05" @default.
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- W2780059547 date "2012-11-20" @default.
- W2780059547 modified "2023-09-25" @default.
- W2780059547 title "Abstract 13592: Contribution of Peripheral versus Central a7-Nicotinic Acetylcholine Receptors to Cardio-protective Effects of Donepezil in Chronic Heart Failure Rats" @default.
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