title: Pyridostigmine blunts the increases in myocardial oxygen demand elicited by the stimulation of the central nervous system in anesthetized rats.
abstract: The purpose of the present work was to verify the effect of pyridostigmine bromide, a reversible cholinesterase inhibitor, on the increases in cardiac work and myocardial oxygen demand produced by central sympathetic stimulation in pentobarbital-anesthetized Wistar rats. The pharmacological stimulation of the central nervous system with L-glutamate (1 mg/kg, intracerebroventricular) elicited marked increases in arterial pressure, dP/dt(max), rate-pressure product, and triple product, reproducing the cardiovascular alterations observed during physical effort and stressful situations. The oral administration of pyridostigmine bromide (5, 10 and 20 mg/kg) 2 hours before central stimulation blunted the increases in mean arterial pressure, dP/dt(max), and triple product elicited by glutamate (29, 28 and 57% for 5 mg/kg; 26, 23 and 46% for 10 mg/kg and 19, 17 and 37% for 20 mg/kg, respectively) when compared to the control group (41, 49 and 106%, respectively; p < 0.05). Our results also showed that the activity of plasmatic cholinesterase was effectively inhibited by pyridostigmine bromide. In conclusion, the increases in endogenous acetylcholine induced by cholinesterase inhibition blunted the centrally-evoked increases in myocardial oxygen demand in anesthetized rats. This effect could represent a cardioprotective action in a situation of ischemic heart disease.
authors.affiliation: Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Grabe-Guimarães
authors.forename: L M
authors.initials: LM
authors.lastname: Alves
authors.forename: E
authors.initials: E
authors.lastname: Tibiriçá
authors.forename: A C
authors.initials: AC
authors.lastname: Nóbrega
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000697:Central Nervous System Stimulants; D002800:Cholinesterase Inhibitors; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D002802:Cholinesterases; D011729:Pyridostigmine Bromide