Abstract：
Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors - pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.
摘要：
乙酰胆碱酯酶抑制剂的慢性治疗可能是治疗心血管疾病的有希望的治疗策略。我们研究的目的是分析使用两种不同的乙酰胆碱酯酶抑制剂治疗14天期间血压（BP）和心率（HR）的变化-仅具有外周作用的吡啶斯的明（PYR）或具有外周和中枢作用的多奈哌齐（DON）。此外,我们研究了它们对血压正常的Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）的心血管对束缚应激的反应以及对HR的交感神经控制的影响。SHR的特征是血压升高和收缩期血压变异性（LF-SBPV）的低频成分增加，但与WKY相比，他们的心脏迷走神经张力和HR变异性（HRV）降低。两种乙酰胆碱酯酶抑制剂的慢性治疗均可降低HR并增加HRV。PYR处理在当天的黑暗阶段略微降低BP和LF-SBPV。两种药物都不能显著改变血压对应激反应,但在束缚应激期间，PYR减弱了HR的增加。关于交感神经平衡，急性甲基阿托品给药导致WKY比SHR更大的HR增加。慢性PYR或DON治疗可增强WKY对甲基阿托品（迷走神经张力）的HRV和HR反应，而PYR而不是DON治疗增强了SHR的HRV和迷走神经张力。总之,与WKY相比，SHR的迷走神经张力较低，但通过两种菌株的慢性PYR治疗均得到增强。因此，慢性外周，但不是中心，乙酰胆碱酯酶抑制对正常血压和高血压大鼠的HR及其变异性都有重要影响。
