Cholinergic stimulation with pyridostigmine increases heart rate variability and baroreflex sensitivity in rats.
OBJECTIVE
Impaired parasympathetic modulation increases the risk for sudden death in patients with heart diseases. Therefore, cholinergic stimulation may have a potential protective role. The aim of this study was to verify the effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, on heart rate (HR), blood pressure (BP), HR and BP variability, and baroreflex sensitivity (BS).


METHODS
Male Wistar rats were divided in two groups: (1) treated with pyridostigmine in drinking water (7 days, n=10; PYR) and (2) a control group (n=12; CTR). BP was recorded in freely moving rats, and HR and BP variability were quantified by the standard deviation (S.D.) of the mean values during a 30-min period and by spectral analysis. BS was assessed by the ratio between pulse interval and BP power spectra (spontaneous BS) and also by the changes on HR produced by phenylephrine and sodium nitroprusside-induced BP changes.


RESULTS
Treated rats had a PYR intake of 7.91+/-1.90 mg/day (approximately 31 mg/kg/day). There were no differences between groups concerning resting HR (P=0.158), systolic BP (P=0.481), and BP variability (P=0.201). On the other hand, treatment with PYR increased HR variability on the time domain (S.D.-PYR: 13.5+/-5.3 ms vs. CTR: 9.9+/-3.6 ms; P=0.034) and frequency domain (Total power--PYR: 208.3+/-157.7 ms(2) vs. CTR: 109.2+/-65.6 ms(2); P=0.030). BS was also augmented with PYR for both the spontaneous method (High frequency band--PYR: 2.55+/-1.06 ms/mm Hg vs. CTR: 1.85+/-0.60 ms/mm Hg; P=0.033) and the drug-induced reflex bradycardia (PYR: 2.48+/-1.02 bpm/mm Hg vs. CTR: 1.54+/-0.58 bpm/mm Hg; P=0.024) and reflex tachycardia (PYR: 4.08+/-1.04 bpm/mm Hg vs. CTR: 2.95+/-1.30 bpm/mm Hg; P=0.037).


CONCLUSIONS
In conclusion, treatment with pyridostigmine increased HR variability and BS in normal rats with no modifications on basal hemodynamic parameters. Considering that reduced HR variability and baroreflex sensitivity are independent risk factors in heart disease, the present results support the concept that cholinergic stimulation with pyridostigmine may become a therapeutic option for vagal dysfunction.
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, Brazil. Pedro.Soares@incor.usp.br
Pedro Paulo da Silva
PP
Soares
Antonio Claudio Lucas
AC
da Nóbrega
Mauro Roberto
MR
Ushizima
Maria Claudia Costa
MC
Irigoyen
D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY
D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide