Pyridostigmine blunts the increases in myocardial oxygen demand elicited by the stimulation of the central nervous system in anesthetized rats.
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.
Grabe-Guimarães
A
A
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Alves
L M
LM
Tibiriçá
E
E
Nóbrega
A C
AC
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
D000697:Central Nervous System Stimulants; D002800:Cholinesterase Inhibitors; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D002802:Cholinesterases; D011729:Pyridostigmine Bromide