Differential regulation of the central neural cardiorespiratory system by metabotropic neurotransmitters

Abstract

Central neurons in the brainstem and spinal cord are essential for the maintenance of sympathetic tone, the integration of responses to the activation of reflexes and central commands, and the generation of an appropriate respiratory motor output. Here, we will discuss work that aims to understand the role that metabotropic neurotransmitter systems play in central cardiorespiratory mechanisms. It is well known that blockade of glutamatergic, gamma-aminobutyric acidergic and glycinergic pathways causes major or even complete disruption of cardiorespiratory systems, whereas antagonism of other neurotransmitter systems barely affects circulation or ventilation. Despite the lack of an 'all-or-none' role for metabotropic neurotransmitters, they are nevertheless significant in modulating the effects of central command and peripheral adaptive reflexes. Finally, we propose that a likely explanation for the plethora of neurotransmitters and their receptors on cardiorespiratory neurons is to enable differential regulation of outputs in response to reflex inputs, while at the same time maintaining a tonic level of sympathetic activity that supports those organs that significantly autoregulate their blood supply, such as the heart, brain, retina and kidney. Such an explanation of the data now available enables the generation of many new testable hypotheses.

Brainstem: neural networks vital for life

“…This facilitates interactions by synaptic transmission and paracrine mediators. Hence, neuromodulators within a particular region of the brainstem rarely affect the cardiovascular system without a concomitant change in breathing or vice versa (Coddou et al 2009;Pilowsky et al 2009). The large numbers of transmitters found in the brainstem enable reflex inputs to regulate motor outputs selectively while maintaining background autonomic motor tone: in addition to acetylcholine, glutamate and gamma-aminobutyric acid (GABA), ionotropic and metabotropic modulators include nicotine, galanin, somatostatin and pituitary adenylate cyclase activating polypeptide (PCAP).…”

Neuroleptic Drugs Affect Sympathetic and Thermogenic Reactions to Orexin A

“…The contemporaneous tachycardia and hyperthermia after an icv injection of orexin A suggest a generalized stimulation of the sympathetic nervous system. Tonically active sympathetic premotor neurons in the rostral ventrolateral medulla project to the intermediolateral cell column of the spinal cord and provide an excitatory input to sympathetic preganglionic neurons so as to maintain the resting level of sympathetic vasomotor tone [9]. The rostral ventrolateral medulla is the key site for cardiovascular homoeostasis.…”

Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure

“…The ability of catestatin pretreatment to enhance barosensitivity and chemosensitivity after PACAP-38 injection supports the hypothesis that catestatin manipulates the intracellular environment within sympathetic neurons in a way that increases responses to PACAP. chromogranin a; sympathetic; baroreflex; chemoreflex; epinephrine HYPERTENSION IS A MAJOR HUMAN health problem that is due, in large part, to increased sympathetic drive that emanates from the rostral ventrolateral medulla (RVLM) (42,44,45). Central neural mechanisms maintain arterial blood pressure by integrating information from reflexes and central behavioral and emotional states to alter efferent sympathetic and parasympathetic activity, according to need (18,44,45).…”

“…chromogranin a; sympathetic; baroreflex; chemoreflex; epinephrine HYPERTENSION IS A MAJOR HUMAN health problem that is due, in large part, to increased sympathetic drive that emanates from the rostral ventrolateral medulla (RVLM) (42,44,45). Central neural mechanisms maintain arterial blood pressure by integrating information from reflexes and central behavioral and emotional states to alter efferent sympathetic and parasympathetic activity, according to need (18,44,45). The RVLM plays a critical role in this system as the final integrative pathway in the regulation of sympathetic tone and cardiovascular adaptive reflexes (e.g., the baroreceptor and chemoreceptor reflexes) (45).…”

“…Central neural mechanisms maintain arterial blood pressure by integrating information from reflexes and central behavioral and emotional states to alter efferent sympathetic and parasympathetic activity, according to need (18,44,45). The RVLM plays a critical role in this system as the final integrative pathway in the regulation of sympathetic tone and cardiovascular adaptive reflexes (e.g., the baroreceptor and chemoreceptor reflexes) (45). The RVLM contains a functionally heterogeneous cell population that includes barosensitive, presympathetic (C1) neurons, which project to sympathetic preganglionic neurons (SPN) in the intermediolateral cell column of the spinal cord.…”