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Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

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Summary

Although the characteristics of the static interactions between the sympathetic and parasympathetic nervous systems in regulating heart rate have been well established, how the dynamic interaction modulates the heart rate response remains unknown. Thus, we investigated the dynamic interaction by estimating the transfer function from nerve stimulation to heart rate, using band-limited Gaussian white noise, in anesthetized rabbits. Concomitant tonic vagal stimulation at 5 and 10Hz increased the gain of the transfer function relating dynamic sympathetic stimulation to heart rate by 55.0% ± 40.1% and 80.7% ± 50.5%, respectively (P < 0.05). Concomitant tonic sympathetic stimulation at 5 and 10Hz increased the gain of the transfer function relating dynamic vagal stimulation to heart rate by 18.2% ± 17.9% and 24.1% ± 18.0%, respectively (P < 0.05). Such bidirectional augmentation was also observed during simultaneous dynamic stimulation of the sympathetic and vagal nerves independent of their stimulation patterns. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic heart rate response to stimulation of the other nerve. We explained this phenomenon by assuming a sigmoidal static relationship between autonomic nerve activity and heart rate. To confirm this assumption, we identified the static and dynamic characteristics of heart rate regulation by a neural network analysis, using large-amplitude Gaussian white noise input. To examine the mechanism involved in the bidirectional augmentation, we increased cytosolic adenosine 3′,5′-cyclic monophosphate (cAMP) at the postjunctional effector site by applying pharmacological interventions. The cAMP accumulation increased the gain of the transfer function relating dynamic vagal stimulation to heart rate. Thus, accumulation of cAMP contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

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References

  1. Rosenblueth A, Freeman NE (1931) The reciprocal innervation in reflex changes of heart rate. Am J Physiol 98:430–434

    Google Scholar 

  2. Glick G, Braunwald E (1964) Relative roles of the sympathetic and parasympathetic nervous systems in the reflex control of heart rate. Circ Res 16:363–375

    Google Scholar 

  3. Levy MN, Zieske H (1969) Autonomic control of cardiac pacemaker activity and atrioventricular transmission. J Appl Physiol 27:465–470

    Google Scholar 

  4. Warner HR, Russell RO (1969) Effect of combined sympathetic and vagal stimulation on heart rate in the dog. Circ Res 24:567–573

    Google Scholar 

  5. Levy MN (1971) Sympathetic-parasympathetic interactions in the heart. Circ Res 29:437–445

    Google Scholar 

  6. Grodner AS, Lahrtz HG, Pool PE, Braunwald E (1970) Neurotransmitter control of sinoatrial pacemaker frequency in isolated rat atria and in intact rabbits. Circ Res 27:867–873

    Google Scholar 

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

    Google Scholar 

  8. Potter EK (1987) Guanethidine blocks neuropeptide-Y-like inhibitory action of sympathetic nerves on cardiac vagus. J Auton Nerv Syst 21:87–90

    Google Scholar 

  9. Revington ML, McCloskey DL (1990) Sympathetic-parasympathetic interactions at the heart, possibly involving neuropeptide Y, in anesthetized dogs. J Physiol 428:359–370

    Google Scholar 

  10. Manabe N, Foldes FF, Töröcsik A, Nagashima H, Goldiner PL, Vizi ES (1991) Presynaptic interaction between vagal and sympathetic innervation in the heart: modulation of acetylcholine and noradrenaline release. J Auton Nerv Syst 32:233–242

    Google Scholar 

  11. Warner MR, Senanayake PD, Ferrario CM, Levy MN (1991) Sympathetic stimulation-evoked overflow of norepinephrine and neuropeptide Y from the heart. Circ Res 69:455–465

    Google Scholar 

  12. Marmarelis PZ, Marmarelis VZ (1978) Analysis of physiological systems. Plenum, New York, pp 131–221

    Google Scholar 

  13. Berger RD, Saul JP, Cohen RJ (1989) Transfer function analysis of autonomic regulation I: Canine atrial rate response. Am J Physiol 256:H142-H152

    Google Scholar 

  14. Kawada T, Ikeda Y, Sugimachi M, Shishido T, Kawaguchi O, Yamazaki T, Alexander J Jr, Sunagawa K (1996) Bidirectional augmentation of heart rate regulation by autonomic nervous system in rabbits. Am J Physiol 271:H288-H295

    Google Scholar 

  15. Brigham EO (1988) The fast Fourier transform and its applications. Prentice-Hall, Englewood Cliffs, pp 167–203

    Google Scholar 

  16. Quarmby LM, Hartzell HC (1995) Molecular biology of G proteins and their role in cardiac excitability. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology, 2nd edn. Saunders, Tokyo, pp 38–48

    Google Scholar 

  17. Warner HR, Cox A (1962) A mathematical model of heart rate control by sympathetic and vagal efferent information. J Appl Physiol 17:349–355

    Google Scholar 

  18. Nakahara T, Kawada T, Sugimachi M, Miyano H, Sato T, Shishido T, Yoshimura R, Miyashita H, Sunagawa K (1998) Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate. Am J Physiol 275:R541-R547

    Google Scholar 

  19. Goldberger JJ, Ahmed MW, Parker MA, Kadish AH (1994) Dissociation of heart rate variability from parasympathetic tone. Am J Physiol 266:H2152-H2157

    Google Scholar 

  20. Kollai M, Koizumi K (1979) Reciprocal and nonreciprocal action of the vagal and sympathetic nerves innervating the heart. J Auton Nerv Syst 1:33–52

    Google Scholar 

  21. Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ (1981) Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213:220–222

    Google Scholar 

  22. Kawada T, Sugimachi M, Shishido T, Miyano H, Ikeda Y, Yoshimura R, Sato T, Takaki H, Alexander J Jr, Sunagawa K (1997) Dynamic vagosympathetic interaction augments heart rate response irrespective of stimulation patterns. Am J Physiol 272:H2180-H2187

    Google Scholar 

  23. Bendat JS, Piersol AG (1971) Random data: analysis and measurement procedures. Wiley-Interscience, New York, pp 147–162

    Google Scholar 

  24. Yang T, Levy MN (1992) Sequence of excitation as a factor in sympathetic-parasympathetic interactions in the heart. Circ Res 71:898–905

    Google Scholar 

  25. Kawada T, Sugimachi M, Shishido T, Miyano H, Sato T, Yoshimura R, Miyashita H, Nakahara T, Alexander J Jr, Sunagawa K (1999) Simultaneous identification of static and dynamic vagosympathetic interactions in regulating heart rate. Am J Physiol 276:R782-R789

    Google Scholar 

  26. Irisawa H, Brown HF, Giles W (1993) Cardiac pacemaking in the sinoatrial node. Physiol Rev 73:197–227

    Google Scholar 

  27. Kameyama M, Hofmann F, Trautwein W (1985) On the mechanism of β-adrenergic regulation of the Ca channel in the guinea-pig heart. Pflügers Arch 405:285–293

    Google Scholar 

  28. Potter EK (1985) Prolonged non-adrenergic inhibition of cardiac vagal action following sympathetic stimulation: neuromodulation by neuropeptide Y? Neurosci Lett 54:117–121

    Google Scholar 

  29. Wetzel GT, Goldstein D, Brown JH (1985) Acetylcholine release from rat atria can be regulated through an α1-adrenergic receptor. Circ Res 56:763–766

    Google Scholar 

  30. Bartel S, Karczewski P, Krause EG (1993) Protein phosphorylation and cardiac function: cholinergic-adrenergic interaction. Cardiovasc Res 27:1948–1953

    Google Scholar 

  31. Biegon RL, Epstein PM, Pappano AJ (1980) Muscarinic antagonism of the effects of a phosphodiesterase inhibitor (methylisobutylxanthine) in embryonic chick ventricle. J Pharmacol Exp Ther 215:348–356

    Google Scholar 

  32. Brown BS, Polson JB, Krzanowski JJ, Wiggins JR (1980) Influence of isoproterenol and methylisobutylxanthine on the contractile and cyclic nucleotide effects of methacholine in isolated rat atria. J Pharmacol Exp Ther 212:325–332

    Google Scholar 

  33. Chang F, Gao J, Tromba C, Cohen I, DiFrancesco D (1990) Acetylcholine reverses effects of β-agonists on pacemaker current in canine cardiac Purkinje fibers but has no direct action. A difference between primary and secondary pacemakers. Circ Res 66:633–636

    Google Scholar 

  34. Han X, Shimoni Y, Giles WR (1994) An obligatory role for nitric oxide in autonomic control of mammalian heart rate. J Physiol (Lond) 476:309–314

    Google Scholar 

  35. Han X, Shimoni Y, Giles WR (1995) A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate. J Gen Physiol 106:45–65

    Google Scholar 

  36. Nakahara T, Kawada T, Sugimachi M, Miyano H, Sato T, Shishido T, Yoshimura R, Miyashita H, Inagaki M, Alexander J Jr, Sunagawa K (1998) Accumulation of cAMP augments dynamic vagal control of heart rate. Am J Physiol 275:H562-H567

    Google Scholar 

  37. Levy MN (1984) Cardiac sympathetic-parasympathetic interactions. Fed Proc 43:2598–2602

    Google Scholar 

  38. Levy MN (1990) Autonomic interactions in cardiac control. Ann NY Acad Sci 601:209–221

    Google Scholar 

  39. Hescheler J, Kameyama M, Trautwein W (1986) On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflügers Arch 407:182–189

    Google Scholar 

  40. Nakajima T, Wu S, Irisawa H, Giles W (1990) Mechanism of acetylcholine-induced inhibition of Ca current in bullfrog atrial myocytes. J Gen Physiol 96:865–885

    Google Scholar 

  41. Petit-Jacques J, Bois P, Bescond J, Lenfant J (1993) Mechanism of muscarinic control of the high-threshold calcium current in rabbit sino-atrial node myocytes. Pflügers Arch 423:21–27

    Google Scholar 

  42. Kelly PA, Balligand JL, Smith TW (1996) Nitric oxide and cardiac function. Circ Res 79:363–380

    Google Scholar 

  43. MacLeon KM (1985) Adrenergic-cholinergic interactions in left atria: interaction of carbachol with alpha- and beta-adrenoceptor agonists. Can J Physiol Pharmacol 64:597–601

    Google Scholar 

  44. Zhang JZ, MacLeod KM (1996) Dissociation of negative inotropic effect of carbachol from changes in cAMP and PKA in perfused rat hearts. Am J Physiol 271:H404-H409

    Google Scholar 

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

    Google Scholar 

  46. McGrattan PA, Brown JH, Brown OM (1987) Parasympathetic effects on in vivo rat heart can be regulated through an α1-adrenergic receptor. Circ Res 60:465–471

    Google Scholar 

  47. Moriarty M, Potter EK, McCloskey DI (1993) Pharmacological separation of cardioaccelerator and vagal inhibitory capacities of sympathetic nerves. J Auton Nerv Syst 43:7–16

    Google Scholar 

  48. Pardini BJ, Lund DD, Puk DE (1992) Site at which neuropeptide Y modulates parasympathetic control of heart rate in guinea pigs and rats. J Auton Nerv Syst 38:139–146

    Google Scholar 

  49. Jalife J, Michaels DC (1985) Phase-dependent interactions of cardiac pacemakers as mechanisms of control and synchronization in the heart. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology and arrhythmias. Grune and Stratton, New York, pp 109–119

    Google Scholar 

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Sunagawa, K., Kawada, T. & Nakahara, T. Dynamic nonlinear vago-sympathetic interaction in regulating heart rate. Heart Vessels 13, 157–174 (1998). https://doi.org/10.1007/BF01745040

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