Acetylcholinesterase Inhibition Attenuates the Development of Hypertension and Inflammation in Spontaneously Hypertensive Rats

Abstract

Background: It is hypothesized that chronic increase of availability of acetylcholine, resulting from the effect of antiacetylcholinesterases, may prevent autonomic imbalance and reduce inflammation yielding benefic effects for cardiovascular disorders in hypertension. The effect of long-term administration of antiacetylcholinesterase agents with central and/or peripheral action, i.e., donepezil and pyridostigmine, were investigated on arterial pressure (AP), sympathovagal balance, plasma cytokine levels, and cardiac remodeling in spontaneously hypertensive rats (SHR).

Methods: Chronic treatment with donepezil or pyridostigmine started before the onset of hypertension. AP was measured by plethysmography every 4 weeks. At the end of 16 weeks of treatment, methylatropine was used to evaluate the cardiac vagal tone; AP and pulse interval (PI) variability were also evaluated followed by plasma and heart collection for analysis.

Results: Pyridostigmine, which does not cross the blood-brain barrier, increased cardiac vagal tone, and reduced cardiomyocyte diameter and collagen density, but did not affect the AP and plasma cytokine levels. Donepezil, which crosses the blood-brain barrier, attenuated the development of hypertension, increased cardiac vagal tone, and improved AP and PI variability. Likewise, donepezil reduced the plasma levels of tumor necrosis factor-α, interleukin 6, and interferon γ, besides reducing cardiomyocyte diameter and collagen density.

Conclusions: Donepezil attenuated the development of hypertension in SHR probably involving antiinflammatory effects, indicating that acetylcholinesterase inhibition yields benefic effects for antihypertensive therapy.

Keywords: autonomic dysfunction; blood pressure; donepezil; hypertension; pharmacological therapy; pyridostigmine; vagal stimulation..