Barosensitive neurons in the rostral ventrolateral medulla of the rat in vivo: Morphological properties and relationship to C1 adrenergic neurons

Lipski, Janusz; Kanjhan, Refik; Kruszewska, Barbara; Smith, Marie-Claire

doi:10.1016/0306-4522(95)92652-z

Cited by 116 publications

(106 citation statements)

References 63 publications

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“…Our data show that PACAP mRNA is present within many neurons in the C1 cell group in both the rostrally projecting (caudal C1) and spinally projecting (rostral C1) parts (4,32). Our finding that caudal C1 neurons (15,36) contain PACAP mRNA confirms the findings of Das et al, (6) who demonstrated PACAP-ir, PNMT-ir neurons at the level of the RVLM that sends projections to the parventricular nucleus. C2 and C3 cell groups also project to the spinal cord (17) and were found to contain PACAP mRNA, but the role of PACAP in these neurons is unknown.…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…[35][36][37] Bilateral muscimol in the RVLM acts on all of the presympathetic neurons, eliminating RVLM-mediated peaks, and unmasks the short-latency spinally mediated peak. In contrast, bilateral SST eliminated only the first RVLM peak, leaving the second largely untouched.…”

Section: Burke Et Al Sstr2a-ir Rvlm Neurons Maintain Blood Pressurementioning

confidence: 99%

“…34 It is thought that the first peak is attributable to activation of fast-conducting presympathetic neurons and the second peak mediated by more slowly conducting catecholaminergic neurons of the RVLM. [35][36][37] Bilateral muscimol in the RVLM acts on all of the presympathetic neurons, eliminating RVLM-mediated peaks, and unmasks the short-latency spinally mediated peak. In contrast, bilateral SST eliminated only the first RVLM peak, leaving the second largely untouched.…”

mentioning

confidence: 99%

Somatostatin 2A Receptor-Expressing Presympathetic Neurons in the Rostral Ventrolateral Medulla Maintain Blood Pressure

Burke

Costin

et al. 2008

Hypertension

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Abstract-Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are critical for the maintenance of sympathetic vasomotor tone and normal cardiovascular reflex function. So far, selectively eliminating/inhibiting distinct subpopulations of RVLM neurons has not significantly altered arterial pressure. Here we show that RVLM presympathetic neurons that express somatostatin 2A receptors are essential for maintaining and potentially generating sympathetic vasomotor tone. Combined immunocytochemistry and in situ hybridization were used to map the expression of somatostatin receptors 1, 2A, 2B, 3, and 4 (sst1 through 4, respectively) in the rat RVLM. sst1 and sst2B were absent; sst3 and sst4 were sparse. However, sst2A was found postsynaptically and detected in 35Ϯ5% of bulbospinal RVLM neurons a population that included 54Ϯ4% of catecholaminergic and 30Ϯ3% of enkephalinergic neurons. Bilateral microinjection into the RVLM of either somatostatin or the receptor-selective agonist lanreotide evoked dramatic, dose-dependent sympathoinhibition, hypotension, and bradycardia that were blocked by the sst2 receptor antagonist BIM-23627 in anesthetized rats. Bilateral RVLM microinjection of somatostatin also attenuated chemoreceptor and somatosympathetic reflex function. Somatostatin only eliminated the first sympathoexcitatory peak evoked by somatosympathetic reflex activation, whereas muscimol abolished both excitatory peaks providing functional evidence that the activity of only a subpopulation of RVLM presympathetic neurons is inhibited by somatostatin. We suggest that the subpopulation of bulbospinal RVLM neurons that expresses the sst2A receptor sets sympathetic vasomotor output. These neurons are essential for maintaining resting blood pressure under anesthesia and contribute to adaptive reflexes mediated through the RVLM. Key Words: cardiovascular Ⅲ sympathetic vasomotor tone Ⅲ catecholamine Ⅲ enkephalin Ⅲ respiration P resympathetic neurons within the rostral ventrolateral medulla (RVLM) contain catecholamines and/or preproenkephalin (PPE) and are critical for the tonic and reflex control of arterial pressure (AP). [1][2][3] Inputs regulating RVLM presympathetic neuronal activity release amino acids and/or a range of modulatory neurochemicals, including peptides. [2][3][4][5][6] These underlie the ability to provide a differentiated sympathetic drive to the various vascular beds, 6 alter the responses to reflex activation, 5 and set the level of AP. 1,3,5 Identification of neurons responsible for generating and maintaining sympathetic vasomotor tone and, therefore, setting the level of AP would be a major breakthrough in understanding circulatory control.The inhibitory neuropeptide somatostatin (SST) is distributed widely in regions of the central nervous system involved in motor, cognitive, autonomic, and neuroendocrine processes. 7,8 Two biologically active forms of SST, SST 14 and SST 28, are cleaved from preprosomatostatin and bind to all of the SST receptors with similar affinity. 8 Six G protein-couple...

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“…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).…”

mentioning

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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Barosensitive neurons in the rostral ventrolateral medulla of the rat in vivo: Morphological properties and relationship to C1 adrenergic neurons

Cited by 116 publications

References 63 publications

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

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

Somatostatin 2A Receptor-Expressing Presympathetic Neurons in the Rostral Ventrolateral Medulla Maintain Blood Pressure

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

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