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1 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, OH, USA; University of Sao Paulo Faculty of Medicine, Ribeirao Preto, SP, Brazil
2 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, OH, USA
3 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, OH, USA; Institute of Normal and Pathological Physiology of Slovak Academy of Sciences, Bratislava, Slovakia (Slovak Republic)
4 University of Sao Paulo Faculty of Medicine, Ribeirao Preto, SP, Brazil
* To whom correspondence should be addressed. E-mail: mariana.morris{at}wright.edu.
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 (10mg/kg/day) 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 as compared to 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, pyridostigmine/stress, stress and pyridostigmine groups, respectively). Baroreflex sensitivity was also increased in the pyridostigmine/stress group (3.6±0.5 ms/mmHg as compared to 1.8 ± 0.3 and 1.7±0.5 ms/mmHg, in 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 PI time series, probably associated with baroreflex input and autonomic drive.
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