title: Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system.
abstract: Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states.
authors.affiliation: Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, IN, USA. Electronic address: ymolkov@iupui.edu.
authors.forename: Yaroslav I
authors.initials: YI
authors.lastname: Molkov
authors.affiliation: Department of Physiology and Pathology, Dentistry School of Araraquara, São Paulo State University, Araraquara, São Paulo, Brazil.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Zoccal
authors.affiliation: Department of Physiological Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Baekey
authors.affiliation: School of Physiology and Pharmacology, Bristol Heart Institute, University of Bristol, Bristol, UK.
authors.forename: Ana P L
authors.initials: AP
authors.lastname: Abdala
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Benedito H
authors.initials: BH
authors.lastname: Machado
authors.affiliation: Departments of Medicine and Neurosciences, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Dick
authors.affiliation: School of Physiology and Pharmacology, Bristol Heart Institute, University of Bristol, Bristol, UK.
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Rybak
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology; D063226:Central Pattern Generators / Q000502:physiology*; D006801:Humans; D012143:Respiratory Physiological Phenomena; D013564:Sympathetic Nervous System / Q000502:physiology*
keywords: baroreflex; chronic intermittent hypoxia; hypertension; modeling; respiratory–sympathetic interactions