Central Command Regulation of Circulatory Function Mediated by Descending Pontine Cholinergic Inputs to Sympathoexcitatory Rostral Ventrolateral Medulla Neurons

Padley, James R.; Kumar, Natasha N.; Li, Qun; Nguyen, Thomas B.; Pilowsky, Paul M.; Goodchild, Ann K.

doi:10.1161/01.res.0000257370.63694.73

Cited by 70 publications

(67 citation statements)

References 56 publications

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“…Experiments were conducted as described previously (10,27,40). Three SHR and three WKY rats were examined to identify neurons in the RVLM that expressed PACAP mRNA and were also immunoreactive (ir) for tyrosine hydroxylase (TH), a marker for catecholaminergic neurons.…”

Section: Combined Ish and Fluorescence Immunohistochemistrymentioning

confidence: 99%

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Farnham

Inglott

Pilowsky

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Farnham MM, Inglott MA, Pilowsky PM. Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 300: H214 -H222, 2011. First published October 15, 2010 doi:10.1152/ajpheart.00662.2010.-The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclaseactivating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6 -38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6 -38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined. sympathetic activity; spinal cord; pituitary adenylate cyclase-activating polypeptide THE ROSTRAL VENTROLATERAL MEDULLA (RVLM) is crucial for the tonic and reflex control of the cardiovascular system (see Refs. 15 and 43 for reviews). RVLM presympathetic neurons are commonly defined as being inhibited following baroreceptor activation and having a spinal axon (2, 28, 29). Neurochemically, 60 -80% of presympathetic neurons are C1 neurons (29,42,48,49), having all of the enzymes required for adrenaline synthesis. Presympathetic RVLM neurons project monosynaptically to sympathetic preganglionic neurons (SPN) in the intermediolateral (IML) cell column of the spinal cord (34,38). SPN, in turn, regulate the activity of the heart, kidneys, blood vessels, and adrenal chromaffin cells, thereby determining sympathetic outflow and ultimately blood pressure.Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory 38-amino-acid peptide originally identified in ovine hypothalamus (32) that also exists as a...

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Section: Combined Ish and Fluorescence Immunohistochemistrymentioning

confidence: 99%

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Farnham

Inglott

Pilowsky

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…The second mechanism is known as "central command". The "central command" consists of forebrain mechanisms (hypothalamic areas) that promote activation of medullary areas involved in cardiorespiratory control (53)(54)(55).…”

Section: Exercise and Central Sympathetic Chemoreflexmentioning

confidence: 99%

Central chemoreceptors and neural mechanisms of cardiorespiratory control

Moreira

Takakura

Damasceno

et al. 2011

Braz J Med Biol Res

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The arterial partial pressure (P CO 2 ) of carbon dioxide is virtually constant because of the close match between the metabolic production of this gas and its excretion via breathing. Blood gas homeostasis does not rely solely on changes in lung ventilation, but also to a considerable extent on circulatory adjustments that regulate the transport of CO 2 from its sites of production to the lungs. The neural mechanisms that coordinate circulatory and ventilatory changes to achieve blood gas homeostasis are the subject of this review. Emphasis will be placed on the control of sympathetic outflow by central chemoreceptors. High levels of CO 2 exert an excitatory effect on sympathetic outflow that is mediated by specialized chemoreceptors such as the neurons located in the retrotrapezoid region. In addition, high CO 2 causes an aversive awareness in conscious animals, activating wakepromoting pathways such as the noradrenergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have projections that contribute to the CO 2 -induced rise in breathing and sympathetic outflow. However, since the level of activity of the retrotrapezoid nucleus is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive, the main focus of the present manuscript is to review the contribution of central chemoreceptors to the control of autonomic and respiratory mechanisms.

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“…Methods were conducted as described previously (13,22). Sense and antisense probes were synthesized by first amplifying a DNA fragment of the PACAP gene from rat brain cDNA (purified DNA showed a single band when run on a 1.2% agarose gel) using forward and reverse primers with Sp6 and T7 promoters attached at the 5Ј end, respectively (PACAP-ISH Fig.…”

Section: Retrograde Cholera Toxin B Subunit Labeling Of Bulbospinal Nmentioning

confidence: 99%

PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo

Farnham¹,

Li²,

Goodchild³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Farnham MMJ, Li Q, Goodchild AK, Pilowsky PM. PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo. Am J Physiol Regul Integr Comp Physiol 294: R1304-R1311, 2008. First published February 13, 2008 doi:10.1152/ajpregu.00753.2007.-Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide present in the rat brain stem. The extent of its localization within catecholaminergic groups and bulbospinal sympathoexcitatory neurons is not established. Using immunohistochemistry and in situ hybridization, we determined the extent of any colocalization with catecholaminergic and/or bulbospinal projections from the brain stem was determined. PACAP mRNA was found in tyrosine hydroxylaseimmunoreactive (TH-ir) neurons in the C1-C3 cell groups. In the rostral ventrolateral medulla (RVLM), PACAP mRNA was found in 84% of the TH-ir neurons and 82% of bulbospinal TH-ir neurons. The functional significance of these PACAP mRNA positive bulbospinal neurons was tested by intrathecal administration of PACAP-38 in anaesthetized rats. Splanchnic sympathetic nerve activity doubled (110%) and heart rate rose significantly (19%), although blood pressure was unaffected. In addition, as previously reported, PACAP was found in the A1 cell group but not in the A5 cell group or in the locus coeruleus. The RVLM is the primary site responsible for the tonic and reflex control of blood pressure through the activity of bulbospinal presympathetic neurons, the majority of which contain TH. The results indicate 1) that pontomedullary neurons containing both TH and PACAP that project to the intermediolateral cell column originate from C1-C3 and not A5, and 2) intrathecal PACAP-38 causes a prolonged, sympathoexcitatory effect.

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Central Command Regulation of Circulatory Function Mediated by Descending Pontine Cholinergic Inputs to Sympathoexcitatory Rostral Ventrolateral Medulla Neurons

Cited by 70 publications

References 56 publications

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Central chemoreceptors and neural mechanisms of cardiorespiratory control

PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo

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