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Autonomic dysfunction and inflammation contribute to the pathophysiology of hypertension. Therefore, an increase in parasympathetic function may have benefic effects during the development of arterial hypertension. We investigated the chronic effect (16 weeks) of the acetylcholinesterase inhibitor donepezil on arterial pressure (AP), heart rate (HR), vagal tone, AP and pulse interval (PI) variability, plasma noradrenaline and pro-inflammatory plasma cytokines in spontaneously hypertensive rats (SHR). DON administration (minipumps, 2 mg/kg/day, n=8) started with SHR aging 5 weeks. Control SHR (n=7) were implanted with empty minipumps. At the end of 16 weeks, femoral AP was recorded in conscious state and methyl atropine provided the evaluation of the vagal tone. Plasma cytokines were analyzed by ELISA. DON promoted: decrease in systolic AP (178±8 vs 202±5 mmHg in control) and HR (304±9 vs 354±13 bpm in control); increase in vagal tone (105±11 vs 64±5 bpm in control); no change of plasma noradrenaline (8.7±0.6 vs 9.1±1.1ng/mL in control); reduction of AP variance (39±7 vs 63±5 mmHg2 in control), power of the low frequency band (LF) of the systolic AP spectrum (4±1 vs 12±3 mmHg2 in control) and LF/HF ratio of PI spectrum (0.2±0.03 vs 0.5±0.005 in control). DON reduced the pro-inflammatory cytokines (pg/mL): TNF-α (22±9 vs 54±5 in control), IFN-γ (11±5 vs 27±5 in control) and IL-6 (22±4 vs 38±5 in control). In conclusion, the increase in parasympathetic function by means of the chronic blockade of acetylcholinesterase with DON improved the cardiovascular autonomic balance and attenuated the inflammatory process during the development of hypertension in SHR.