Enhanced heart rate variability and baroreflex index after stress and cholinesterase inhibition in mice.
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.
Department of Pharmacology and Toxicology, Wright State University School of Medicine, 3640 Colonel Glenn Hwy., Dayton, OH 45435, USA.
Luis F
LF
Joaquim
Vera M
VM
Farah
Iveta
I
Bernatova
Rubens
R
Fazan
Robert
R
Grubbs
Mariana
M
Morris
D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011674:Pulse; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D013312:Stress, Physiological / Q000503:physiopathology*
D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide