PS-B10-5: EFFECTS OF CHRONIC ACETYLCHOLINESTERASE INHIBITION WITH PYRIDOSTIGMINE ON CARDIOVASCULAR SYSTEM AND AUTONOMIC BALANCE IN SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Objective: The imbalance in autonomic nervous system, characterized by increased sympathetic and attenuated parasympathetic activity, plays an important role in the pathogenesis of hypertension. The spontaneously hypertensive rats (SHR) which are one of the most studied animal models of essential hypertension, are characterized by autonomic nervous system imbalance. Our study was aimed to determine the effect of chronic inhibition of acetylcholinesterase with pyridostigmine on cardiovascular parameters and sympatho-vagal balance in SHR and Wistar-Kyoto (WKY) rats. Design and method: Adult male SHR and WKY rats were treated with pyridostigmine (25 mg/kg/day) in drinking solution for 2 weeks. The rats were implanted with telemetric transducers to measure blood pressure (BP) and heart rate (HR). Autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Sympatho-vagal balance was also evaluated pharmacologically by administration of methylatropine (antagonist of muscarinic acetylcholine receptors) and propranolol (antagonist of beta-adrenergic receptors) in a separate set of rats. Results: SHR have elevated BP, increased vascular sympathetic activity (low frequency component of SBPV), and reduced HRV compared to WKY. Pyridostigmine significantly reduced HR in rats of both strains (during both dark and light phase) and BP during the dark (active) phase compared to untreated controls. Acetylcholinesterase activity in plasma was significantly reduced by pyridostigmine treatment in both strains (SHR 53 ± 3%, WKY 46 ± 3%). Sympatho-vagal balance examination revealed reduced cardiac vagal tone in SHR as evidenced by blunted HR response to the muscarinic receptor blocker methylatropine and increased cardiac sympathetic tone as evidenced by elevated HR response to the beta-blocker propranolol. Pyridostigmine treatment increased cardiac vagal tone and decreased cardiac sympathetic tone in SHR to the levels of untreated WKY. Moreover, pyridostigmine increased HRV and reduced low frequency component of SBPV in SHR indicating the restoration of autonomic balance. The reduction of sympathetic tone in pyridostigmine-treated rats was also evident from the reduction of plasma levels of noradrenaline. The potentiation of cardiac parasympathetic activity by pyridostigmine treatment was confirmed by the attenuation of restraint stress-induced tachycardia in both strains. Conclusions: Chronic stimulation of peripheral cholinergic system with pyridostigmine leads to the improvement of autonomic nervous system balance in SHR by increasing cardiac vagal tone and reducing sympathetic tone. Thus, chronic treatment with acetylcholinesterase inhibitors seems to be a promising therapeutic strategy for the restoration of autonomic balance in cardiovascular diseases.