Donepezil attenuates progression of cardiovascular remodeling and improves prognosis in spontaneously hypertensive rats with chronic myocardial infarction.
Hypertens Res
; 47(5): 1298-1308, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38485776
ABSTRACT
The acetylcholinesterase inhibitor donepezil restores autonomic balance, reduces inflammation, and improves long-term survival in rats with chronic heart failure (CHF) following myocardial infarction (MI). As arterial hypertension is associated with a significant risk of cardiovascular death, we investigated the effectiveness of donepezil in treating CHF in spontaneously hypertensive rats (SHR). CHF was induced in SHR by inducing permanent MI. After 2 weeks, the surviving SHR were randomly assigned to sham-operated (SO), untreated (UT), or oral donepezil-treated (DT, 5 mg/kg/day) groups, and various vitals and parameters were monitored. After 7 weeks of treatment, heart rate and arterial hypertension reduced significantly in DT rats than in UT rats. Donepezil treatment improved 50-day survival (41% to 80%, P = 0.004); suppressed progression of cardiac hypertrophy, cardiac dysfunction (cardiac index 133 ± 5 vs. 112 ± 5 ml/min/kg, P < 0.05; left ventricular end-diastolic pressure 12 ± 3 vs. 22 ± 2 mmHg, P < 0.05; left ventricular +dp/dtmax 5348 ± 338 vs. 4267 ± 114 mmHg/s, P < 0.05), systemic inflammation, and coronary artery remodeling (wall thickness 26.3 ± 1.4 vs. 34.7 ± 0.7 µm, P < 0.01; media-to-lumen ratio 3.70 ± 0.73 vs. 8.59 ± 0.84, P < 0.001); increased capillary density; and decreased plasma catecholamine, B-type natriuretic peptide, arginine vasopressin, and angiotensin II levels. Donepezil treatment attenuated cardiac and coronary artery remodeling, mitigated cardiac dysfunction, and significantly improved the prognosis of SHR with CHF.
Key words
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Piperidines
/
Rats, Inbred SHR
/
Ventricular Remodeling
/
Donepezil
/
Indans
/
Myocardial Infarction
Limits:
Animals
Language:
En
Journal:
Hypertens Res
Year:
2024
Document type:
Article