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Pyridostigmine blunts the increases in myocardial oxygen demand elicited by the stimulation of the central nervous system in anesthetized rats

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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 pentobarbitalanesthetized Wistar rats. The pharmacological stimulation of the central nervous system with L-glutamate (1 mg/kg, intracerebroventricular) elicited marked increases in arterial pressure, dP/dtmax, 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/dtmax, 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 cetrally-evoked increases in myocardial oxygen demand in anesthetized rats. This effect could represent a cardioprotective action in a situation of ischemic heart disease.

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References

  1. Bilman GE, Schwartz PJ, Tone HL. Baroreceptor reflex control of heart rate: a predictor of sudden cardiac death.Circulation 1984; 66:874–881.

    Google Scholar 

  2. Schwartz PJ, La Rovere MT, Vanoli E. Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification.Circulation 1992; 85(Suppl 1):177–199.

    Google Scholar 

  3. Odemuyiwa O, Malik M, Farrell T, Bashir Y, Poloniecki J, Camm J. Comparision of the predictive characteristics of the heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction.Am J Cardiol 1991; 68:434–439.

    Article  CAS  PubMed  Google Scholar 

  4. La Rovere MT, Bigger JT Jr, Marcus Fl, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators.Lancet 1998; 351:478–484.

    Google Scholar 

  5. Eliakim M, Bellet S, Tawil E, Muller O. Effect of vagal stimulation and acetylcholine on the ventricle: studies in dogs with complete heart block.Circ Res 1961; 9:1372–1379.

    CAS  PubMed  Google Scholar 

  6. Waxman MB, Cupps CL, Cameron DA. Modulation of an idioventricular rhythm by vagal tone.J Am Coll Cardiol 1988; 11:1052–1060.

    CAS  PubMed  Google Scholar 

  7. Schwartz PJ, Verrier RL, Lown B. Effect of stellectomy and vagotomy on ventricular refractoriness.Circ Res 1977; 40:536–540.

    CAS  PubMed  Google Scholar 

  8. Martins JB, Zipes DP. Effects of sympathetic and vagal nerves on recovery properties of the endocardium and epicardium of the canine left ventricle.Circ Res 1980; 46:100–110.

    CAS  PubMed  Google Scholar 

  9. De Ferrari GM, Salvati P, Grossoni M, et al. Pharmacologic modulation of the autonomic nervous system in the prevention of sudden cardiac death. A study with propranolol, methacoline and oxotremorine in conscious dogs with a healed myocardial infarction.J Am Coll Cardiol 1993; 21:283–290.

    Google Scholar 

  10. Hollenberg M, Carriere S, Barger AC. Biphasic action of acetylcholine on ventricular myocardium.Circ Res 1965; 16:527–536.

    CAS  PubMed  Google Scholar 

  11. Levy MN, Zieske H. Comparision of the cardiac effects of vagus nerve stimulation and acetylcholine infusions.Am J Physiol 1969; 216:890–897.

    CAS  PubMed  Google Scholar 

  12. Higgins CB, Vatner SF, Braunwald E. Parasympathetic control of the heart.Pharmacol Rev 1973; 25:119–155.

    CAS  PubMed  Google Scholar 

  13. Löffelholz K, Pappano AJ. The parasympathetic neuroeffector junction of the heart.Pharmacol Rev 1985; 37:1–24.

    PubMed  Google Scholar 

  14. Tibiriçá E, Monassier L, Feldman J, Brandt C, Verdun A, Bousquet P. Baclofen prevents the increase of myocardial oxygen demand indexes evoked by the hypothalamic stimulation in rabbits.Naunyn Schmiedeberg's Arch Pharmacol 1993; 348:164–171.

    Google Scholar 

  15. Tibiriçá E, Catelli M, Lessa MA, Roegel JC, Monassier L, Bousquet P. Inhibition of centrally induces increase in myocardial oxygen demand in rabbits by chronic treatment with baclofen, a selective GABAB agonist.Br J Pharmacol 1995; 115:1331–1335.

    PubMed  Google Scholar 

  16. Magnotti Jr RA, Eberly JP, Quarm DE and McConnell RS. Measurement of acetylcholinesterase in erythrocytes in the field.Clin Chem 1987; 33:1731–1735.

    CAS  PubMed  Google Scholar 

  17. Azevedo AD, Hilton SM, Timms RJ. The defence reaction elicited by midbrain and hypothalamic stimulation in the rabbit.J Physiol London 1980; 301:56P-57P.

    Google Scholar 

  18. Resnik H, Mason MF. The effect of the injection of certain nitrogencontaining compounds into the cisterna magna on the blood pressure of dogs.Am J Med Sci 1936; XX:520–525.

    Google Scholar 

  19. Lown B, Verrier RL, Rabinowitz SH. Neural and psychologic mechanisms and the problem of sudden cardiac death.Am J Cardiol 1977; 39:890–972.

    CAS  PubMed  Google Scholar 

  20. Reich P, Da Silva DA, Lown B, Murawski J. Acute psychological disturbance preceeding life-threatening ventricular arrhythmias.JAMA 1981; 246:233–235.

    Article  CAS  PubMed  Google Scholar 

  21. Specchia G, De Servi S, Falcone C, et al. Mental arithmetic stress testing in patients with coronary artery disease.Am Heart J 1984; 108:56–63.

    Article  CAS  PubMed  Google Scholar 

  22. Monassier L, Tibiriçá E, Roegel JC, Mettauer B, Feldman J, Bousquet P. Prevention by NMDA receptor antagonists of the centrallyevoked increases of cardiac inotropic responses in rabbits.Br J Pharmacol 1994; 111:1347–1354.

    CAS  PubMed  Google Scholar 

  23. Taylor P. Anticholinesterase agents. In: Hardman JG and Limbird LE (Editor-in-Chief). Goodman and Gilman'sThe Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 1996;161–176.

    Google Scholar 

  24. Tseng CJ, Appalsamy M, Robertson D, Mosqueda-Garcia. Effects of nicotine on brain stem mechanisms of cardiovascular control.J Pharmacol Exp Ther 1993, 265:1511–1518.

    CAS  PubMed  Google Scholar 

  25. Nóbrega ACL, Carvalho ACG, Bastos BG. Resting and reflex heart rate responses during cholinergic stimulation with pyridostigmine in humans.Braz J Med Biol Res 1996; 29:1461–1465.

    PubMed  Google Scholar 

  26. Stephenson LA, Kolka MA. Acetylcholinesterase inhibitor, pyridostigmine bromide, reduces skin blood flow in humans.Am J Physiol 1990; 258 (4 Pt 2):R951-R957.

    CAS  PubMed  Google Scholar 

  27. Reis AF, Moraes RS, Bastos BG, Ferlin E, Ribeiro JP, Nóbrega ACL. Heart rate variability during cholinergic stimulation with pyridostigmine in healthy subjects.J Am Coll Cardiol 1998; 31:407C.

    Google Scholar 

  28. Izraeli S, Alcalay M, Benjamini Y, Wallach-Kapon R, Tochner Z, Akselrod S. Modulation of the dose-dependent effects of atropine by low-dose pyridostigmine: quantification by spectral analysis of heart rate fluctuations in healthy human beings.Pharmacol Biochem Behav 1991; 39:613–617.

    Article  CAS  PubMed  Google Scholar 

  29. Pontes PV, Bastos BG, Mesquita ET, Nóbrega ACL. Cholinergic stimulation with pyridostigmine: echocardiographic analysis in healthy subjects.J Am Coll Cardiol 1998; 31:433C.

    Google Scholar 

  30. Thaulow E, Erikssen JE. How important is heart rate?J Hypertension 1991;9(suppl.):S27-S30.

    CAS  Google Scholar 

  31. Nóbrega ACL, Carvalho ACG, Santos KB, Soares PPS. Cholinergic stimulation with pyridostigmine blunts the cardiac reponses to mental stress.Clin Auton Res 1999; 9:11–16.

    Google Scholar 

  32. Löffelholz K, Muscholl E. Inhibition by parasympathetic nerve stimulation of the release of the adrenergic transmitter.Naunyn Schmiedeberg's Arch Pharmacol 1970; 267:181–184.

    Google Scholar 

  33. Yang ZK, Boyett MR, Janvier SO, McMorn SO, Shui Z, Karim F. Regional differences in the negative inotropic effect of acetylcholine within the canine ventricle.J Physiol 1996; 492(3):789–806.

    CAS  PubMed  Google Scholar 

  34. Levy MN, Blattberg B. Effect of vagal stimulation on the overflow of norepinephrine into the coronary sinus during cardiac sympathetic nerve stimulation in the dog.Circ Res 1976; 38:81–85.

    CAS  PubMed  Google Scholar 

  35. Muscholl E. Peripheral muscarinic control of norepinephrine release in the cardiovascular system.Am J Physiol 1980; 239:H713-H720.

    CAS  PubMed  Google Scholar 

  36. Koumi SI, Sato R, Nagasawa K, Hayakawa H. Activation of inwardly rectifying channels by muscarinic receptor-linked G protein in isolated human ventricular myocytes.J Membrane Biol 1997; 157:71–81.

    CAS  Google Scholar 

  37. Gao J, Mathias RT, Cohen IS, Baldo GJ. Effects of acetylcholine on the Na+−K+ pump corrent in guinea-pig ventricular myocytes.J Physiol 1997; 501(3):527–535.

    Article  CAS  PubMed  Google Scholar 

  38. Bailey JC, Greenspan K, Elizari MV, Anderson GJ, Fisch C. Effects os acetylcholine on automaticity and conduction the proximal portion of the His-Purkinje specialized conduction system of the dog.Circ Res 1972; 30:210–216

    CAS  PubMed  Google Scholar 

  39. Bailey JC, Watanabe AM, Besh HR jr, Lathrop DA. Acetylcholine antagonism of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers.Circ Res 1979; 44:378–383.

    CAS  PubMed  Google Scholar 

  40. Litovsky SH, Antzelevitch C. Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol. A direct effect of acetylcholine in ventricular myocardium.Circ Res 1990; 67:615–627.

    CAS  PubMed  Google Scholar 

  41. Kent KM, Smith ER, Redwood DR, Epstein SE. Electrical stability of acutely ischemic myocardium: influences of heart rate and vagal stimulation.Circulation 1973; 47:291–298.

    CAS  PubMed  Google Scholar 

  42. Waxman MB, Wald RW. Termination of ventricular tachycardia by increase in cardiac vagal drive.Circulation 1977; 56:385–391.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, MG, Brazil

    Andrea Grabe-Guimarães M.Sc.

  2. Departamento de Fisiologia, Instituto Biomédico, Universidade Federal Fluminense, Niterói, RJ, Brazil

    Antonio C. L. Nóbrega M.D., Ph.D.

  3. Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365-Manguinhos, Caixa Postal 926, 21045-900, Rio de Janeiro, RJ, Brazil

    Andrea Grabe-Guimarães M.Sc., Leandro M. Alves B.Sc. &  Eduardo Tibiriçá M.D., Ph.D.

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  1. Andrea Grabe-Guimarães M.Sc.
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  2. Leandro M. Alves B.Sc.
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  3. Eduardo Tibiriçá M.D., Ph.D.
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  4. Antonio C. L. Nóbrega M.D., Ph.D.
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Correspondence to Eduardo Tibiriçá M.D., Ph.D..

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Grabe-Guimarães, A., Alves, L.M., Tibiriçá, E. et al. Pyridostigmine blunts the increases in myocardial oxygen demand elicited by the stimulation of the central nervous system in anesthetized rats. Clinical Autonomic Research 9, 83–89 (1999). https://doi.org/10.1007/BF02311764

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  • DOI: https://doi.org/10.1007/BF02311764

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