Joaquim Luis F, Farah Vera M, Bernatova Iveta, Fazan Rubens, Grubbs Robert, Morris Mariana
Department of Pharmacology and Toxicology, Wright State University School of Medicine, 3640 Colonel Glenn Hwy., Dayton, OH 45435, USA.
Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H251-7. doi: 10.1152/ajpheart.01136.2003. Epub 2004 Feb 26.
Experiments tested the effect of stress coupled with cholinesterase inhibition on blood pressure, heart rate, baroreflex index, and variability in time and frequency domain in conscious mice. The objective was to determine whether cholinergic systems interact with stress to alter cardiovascular responses. Male C57BL/6J mice with arterial catheters were exposed to 3-day treatments: 1) intermittent shaker stress, 2) pyridostigmine (10 mg.kg(-1).day(-1)); or 3) combined pyridostigmine and stress. Pyridostigmine reduced blood cholinesterase (-33%) with no added effects of stress. Twenty-four-hour blood pressure recordings showed that there were no differences in blood pressure and heart rate with the treatments. Pulse interval standard deviation was greatly increased in the pyridostigmine/stress group compared with stress or pyridostigmine groups (11.0 +/- 1.4, 5.0 +/- 0.9, and 7.5 +/- 0.9 ms, respectively). Spectral analysis showed two distinct components for pulse interval variability (low and high frequency). Variability in the low-frequency range was greatly enhanced in the pyridostigmine/stress group, seen as a doubling of the power (9.5 +/- 1.7, 3.3 +/- 0.9, and 5.0 +/- 0.6 ms for pyridostigmine/stress, stress and pyridostigmine groups, respectively). Baroreflex sensitivity was also increased in the pyridostigmine/stress group (3.6 +/- 0.5 compared with 1.8 +/- 0.3 and 1.7 +/- 0.5 ms/mmHg in the stress and pyridostigmine groups, respectively). There was no difference in blood pressure variability or its spectral components. Results demonstrate that there are potent interactions between a mild stressor and cholinesterase inhibition seen as an accentuation of low-frequency variability in pulse interval time series, probably associated with baroreflex input and autonomic drive.
实验测试了应激与胆碱酯酶抑制相结合对清醒小鼠血压、心率、压力反射指数以及时域和频域变异性的影响。目的是确定胆碱能系统是否与应激相互作用以改变心血管反应。对植入动脉导管的雄性C57BL/6J小鼠进行为期3天的处理:1)间歇性摇晃应激,2)吡啶斯的明(10 mg·kg⁻¹·天⁻¹);或3)吡啶斯的明与应激联合处理。吡啶斯的明降低了血液胆碱酯酶(-33%),应激无额外影响。24小时血压记录显示,各处理组的血压和心率无差异。与应激组或吡啶斯的明组相比,吡啶斯的明/应激组的脉搏间期标准差大幅增加(分别为11.0±1.4、5.0±0.9和7.5±0.9 ms)。频谱分析显示脉搏间期变异性有两个不同的成分(低频和高频)。吡啶斯的明/应激组低频范围内的变异性大幅增强,表现为功率加倍(吡啶斯的明/应激组、应激组和吡啶斯的明组分别为9.5±1.7、3.3±0.9和5.0±0.6 ms)。吡啶斯的明/应激组的压力反射敏感性也增加(分别为3.6±0.5,而应激组和吡啶斯的明组分别为1.8±0.3和1.7±0.5 ms/mmHg)。血压变异性及其频谱成分无差异。结果表明,轻度应激源与胆碱酯酶抑制之间存在显著相互作用,表现为脉搏间期时间序列中低频变异性的增强,这可能与压力反射输入和自主神经驱动有关。