Exercise and pyridostigmine prevents gastric emptying delay and increase blood pressure and cisplatin-induced baroreflex sensitivity in rats

Life Sci. 2021 Feb 15:267:118972. doi: 10.1016/j.lfs.2020.118972. Epub 2020 Dec 29.

Abstract

Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces improves in the autonomic nervous system. In the current study, we investigated the effect of physical exercise and pyridostigmine treatment on gastrointestinal and cardiovascular changes in cisplatin-treated rats. Rats were divided into groups: Saline (S), Cisplatin (Cis), Exercise (Ex), Cisplatin+Exercise (Cis+Ex), Pyridostigmine (Pyr), and Cisplatin+Pyridostigmine (Cis+Pyr). We induced gastrointestinal dysmotility by administering 3 mg kg-1 of cisplatin once week for 5 weeks. The Ex was swimming (1 h per day/5 days per week for 5 weeks with 5% b.w.). GE was evaluated through the colorimetric method of fractional red phenol recovery 10 min after feeding. Pyr groups received 1.5 mg kg-1, p.o. or concomitant Cis treatment. Moreover, gastric contraction in vitro and hemodynamic parameters such as MAP, HR, and evoked baroreflex sensitivity were assessed, as well as sympathetic and parasympathetic tone and intrinsic heart rate (IHR). Cis decrease GE vs. saline (p<0.05). Cis+Ex or Cis+Pyr prevented (p<0.05) decrease in GE vs. Cis rats. Cis decreased (p<0.05) gastric responsiveness in vitro vs. saline. Cis+Ex or Cis+Pyr prevented this phenomenon. Cis treatment increase MAP and decrease in HR (p<0.05) vs saline. Cis+Ex or Cis+Pyr attenuated (p<0.05) both alterations. Cis increased sympathetic tone and decreased vagal tone and IHR (p<0.05) vs. the saline. Cis+Ex or Cis+Pyr prevented those effects vs. the Cis group. In conclusion, physical exercise and pyridostigmine treatment improves autonomic dysfunction and prevented GE delay and changes in hemodynamic parameters, baroreflex sensitivity, and cardiac autonomic control in cisplatin-treated rats.

Keywords: Baroreflex; Blood pressure; Cisplatin; Exercise; Gastric dysmotility; Pyridostigmine.

MeSH terms

  • Animals
  • Autonomic Nervous System / physiopathology
  • Baroreflex / drug effects*
  • Baroreflex / physiology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cardiovascular System / physiopathology
  • Cisplatin / adverse effects
  • Cisplatin / pharmacology
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology
  • Heart / drug effects
  • Heart Rate / drug effects
  • Male
  • Myocardial Infarction / physiopathology
  • Physical Conditioning, Animal / physiology*
  • Pyridostigmine Bromide / pharmacology*
  • Rats
  • Rats, Wistar
  • Vagus Nerve / drug effects

Substances

  • Pyridostigmine Bromide
  • Cisplatin