Sympathoinhibition from ventrolateral periaqueductal gray mediated by 5-HT1A receptors in the RVLM

2001 ◽  
Vol 280 (4) ◽  
pp. R976-R984 ◽  
Author(s):  
M. Bago ◽  
C. Dean
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Pressor Response ◽  
Periaqueductal Gray ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Pentobarbital Sodium ◽  
Arterial Blood ◽  
Way 100635

The role of 5-hydroxytryptamine 1A (5-HT1A) receptors located in the rostral ventrolateral medulla (RVLM) in the mediation of a sympathoinhibitory and depressor response elicited from the ventrolateral periaqueductal gray (vlPAG) matter of the midbrain was examined in pentobarbital sodium-anesthetized rats. Activation of neurons in the vlPAG evoked a decrease in renal and lumbar sympathetic nerve activities and a decrease in arterial blood pressure. After microinjection of the specific 5-HT1A-receptor antagonist WAY-100635 into the pressor area of the RVLM, the vlPAG-evoked sympathoinhibition and hypotension was attenuated to control levels (7 of 15 animals) or converted into a sympathoexcitation and pressor response (8 of 15 animals). Baroreflex inhibition of sympathetic nerve activity was not impaired by microinjection of WAY into the sympathoexcitatory region of the RVLM. These data suggest that sympathoinhibition and hypotension elicited by activation of neurons in the vlPAG are mediated by 5-HT1A receptors in the RVLM.

scholarly journals Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

2012 ◽  
Vol 302 (11) ◽  
pp. H2419-H2427 ◽  
Author(s):  
Lauro C. Vianna ◽  
Emma C. Hart ◽  
Seth T. Fairfax ◽  
Nisha Charkoudian ◽  
Michael J. Joyner ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Sympathetic Nerve ◽  
Healthy Aging ◽  
Sympathetic Nerve Activity ◽  
Pressor Response ◽  
Muscle Sympathetic Nerve Activity ◽  
Older Men ◽  
Nerve Activity ◽  
Arterial Blood ◽  
Age And Sex

The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate BP on a beat-to-beat basis is affected by age or sex. BP and MSNA were measured during supine rest in 40 young (20 men) and 40 older (20 men) healthy subjects. Beat-to-beat fluctuations in mean arterial pressure (MAP) were characterized for 15 cardiac cycles after each MSNA burst using signal averaging. The rise in MAP following an MSNA burst was similar between young men and women (+2.64 ± 0.3 vs. +2.57 ± 0.3 mmHg, respectively). However, the magnitude of the increase in MAP after an MSNA burst was reduced in older compared with young subjects ( P < 0.05). Moreover, the attenuation of the pressor response was greater in older women (+1.20 ± 0.1 mmHg) compared with older men (+1.72 ± 0.2 mmHg; P < 0.05). Interestingly, in all groups, MAP consistently decreased after cardiac cycles without MSNA bursts (nonbursts) with the magnitude of fall greatest in older men. In summary, healthy aging is associated with an attenuated beat-to-beat increase in BP after a spontaneous MSNA burst, and this attenuation is more pronounced in postmenopausal women. Furthermore, our nonburst findings highlight the importance of sympathetic vasoconstrictor activity to maintain beat-to-beat BP, particularly in older men.

scholarly journals Renal sympathoinhibition mediated by 5-HT1Areceptors in the RVLM during severe hemorrhage in rats

2002 ◽  
Vol 282 (1) ◽  
pp. R122-R130 ◽  
Author(s):  
C. Dean ◽  
M. Bago
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Arterial Blood ◽  
Severe Hemorrhage ◽  
Renal Sympathetic

The role of 5-hydroxytryptamine type 1A (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) in the mediation of the sympathoinhibitory and hypotensive responses to severe hemorrhage was examined in pentobarbital sodium-anesthetized rats. The control response to hemorrhage (1 ml/min to 50 mmHg) consisted of a fall in arterial blood pressure and an initial baroreflex increase in renal sympathetic nerve activity followed after 2 min by a rapid decline in blood pressure accompanied by a decrease in renal sympathetic nerve activity. In response to hemorrhage in animals in which the specific 5-HT1A receptor antagonist WAY-100635 was microinjected into the pressor area of the RVLM, the fall in blood pressure was delayed and attenuated while renal sympathetic nerve activity was increased and maintained above baseline. In barodenervated animals with blockade of RVLM 5-HT1A receptors, there was no change in renal sympathetic nerve activity in response to hemorrhage. These data suggest that renal sympathoinhibition elicited in response to severe hemorrhage is mediated by 5-HT1A receptors in the RVLM.

Sympathoinhibition from ventrolateral periaqueductal gray mediated by the caudal midline medulla

2005 ◽  
Vol 289 (5) ◽  
pp. R1477-R1481 ◽  
Author(s):  
C. Dean
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Periaqueductal Gray ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Depressor Response ◽  
Arterial Blood ◽  
Renal Sympathetic

Activation of neurons in the ventrolateral region of the periaqueductal gray (vlPAG) can elicit a decrease in renal sympathetic nerve activity and blood pressure. The present study investigated whether the vlPAG-evoked sympathoinhibitory response depends on neurons in the caudal midline medulla (CMM). In pentobarbital-anesthetized rats, activation of neurons in the vlPAG evoked a decrease in renal sympathetic nerve activity to 29.4 ± 4.8% below baseline levels and arterial blood pressure fell 8.9 ± 1.6 mmHg ( n = 20). Microinjection of the GABA agonist muscimol into sympathoinhibitory regions of the CMM significantly attenuated the vlPAG-evoked sympathoinhibition to 17.9 ± 4.1% below baseline and the depressor response to 4.3 ± 1.2 mmHg. At 65% (13/20) of the sites examined, the vlPAG-evoked sympathoinhibition was responsive to CMM muscimol microinjection and attenuated from 34.2% to 11.5%, with the depressor response reduced from 14.8 to 3 mmHg. Microinjection of muscimol at the remaining 35% of the CMM sympathoinhibitory sites was ineffective on the vlPAG-evoked sympathoinhibition and depressor response. These data indicate that sympathoinhibitory and hypotensive responses elicited by activation of neurons in the vlPAG can be mediated by neurons in the sympathoinhibitory region of the CMM. The finding that the vlPAG-evoked response is not affected by muscimol at all CMM sympathoinhibitory sites also suggests that sympathoinhibitory sites in the CMM are not homogeneous and can mediate functionally different responses.

scholarly journals Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats

2012 ◽  
Vol 303 (3) ◽  
pp. R301-R310 ◽  
Author(s):  
Le Gui ◽  
Lila P. LaGrange ◽  
Robert A. Larson ◽  
Mingjun Gu ◽  
Jianhua Zhu ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Channel Blocker ◽  
Dependent Manner ◽  
Sk Channels ◽  
Nerve Activity ◽  
Arterial Blood ◽  
Sk Channel ◽  
Small Conductance

Small conductance Ca2+-activated K+ (SK) channels regulate membrane properties of rostral ventrolateral medulla (RVLM) projecting hypothalamic paraventricular nucleus (PVN) neurons and inhibition of SK channels increases in vitro excitability. Here, we determined in vivo the role of PVN SK channels in regulating sympathetic nerve activity (SNA) and mean arterial pressure (MAP). In anesthetized rats, bilateral PVN microinjection of SK channel blocker with peptide apamin (0, 0.125, 1.25, 3.75, 12.5, and 25 pmol) increased splanchnic SNA (SSNA), renal SNA (RSNA), MAP, and heart rate (HR) in a dose-dependent manner. Maximum increases in SSNA, RSNA, MAP, and HR elicited by apamin (12.5 pmol, n = 7) were 330 ± 40% ( P < 0.01), 271 ± 40% ( P < 0.01), 29 ± 4 mmHg ( P < 0.01), and 34 ± 9 beats/min ( P < 0.01), respectively. PVN injection of the nonpeptide SK channel blocker UCL1684 (250 pmol, n = 7) significantly increased SSNA ( P < 0.05), RSNA ( P < 0.05), MAP ( P < 0.05), and HR ( P < 0.05). Neither apamin injected outside the PVN (12.5 pmol, n = 6) nor peripheral administration of the same dose of apamin (12.5 pmol, n = 5) evoked any significant changes in the recorded variables. PVN-injected SK channel enhancer 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO, 5 nmol, n = 4) or N-cyclohexyl- N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidin]amine (CyPPA, 5 nmol, n = 6) did not significantly alter the SSNA, RSNA, MAP, and HR. Western blot and RT-PCR analysis of punched PVN tissue showed abundant expression of SK1-3 channels. We conclude that SK channels expressed in the PVN play an important role in the regulation of sympathetic outflow and cardiovascular function.

Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia

1995 ◽  
Vol 79 (2) ◽  
pp. 581-588 ◽  
Author(s):  
U. Leuenberger ◽  
E. Jacob ◽  
L. Sweer ◽  
N. Waravdekar ◽  
C. Zwillich ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Matched Control ◽  
Sleep Stage ◽  
Muscle Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Obstructive Apnea ◽  
Arterial Blood ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is associated with oscillations of arterial blood pressure (BP) that occur in phase with irregularities of respiration. To explore the role of the sympathetic nervous system in these responses, we studied muscle sympathetic nerve activity (MSNA; peroneal microneurography), an index of vasoconstrictor nerve traffic, and BP during awake regular breathing and during spontaneous apneas in patients with OSA. To determine the role of the arterial chemoreflex, we also examined the effects of 100% O2 (hyperoxia) on MSNA and BP. In awake regularly breathing patients with OSA (n = 12), resting MSNA was markedly higher than in an age-matched control population (n = 15) [41 +/- 23 (SD) vs. 24 +/- 17 bursts/min; P < 0.05] and was unchanged during hyperoxia (n = 9). Apneas during sleep (n = 8) were associated with surges in MSNA followed by transient rises in BP when breathing resumed. In contrast to room air apneas, hyperoxic apneas of similar duration were associated with attenuated MSNA responses (+82 +/- 84% vs. +5 +/- 25% compared with awake baseline; P < 0.05; n = 6), even though O2 did not affect sleep stage and the occurrence of arousal. Thus the BP oscillations that occur with apnea during sleep may in part be mediated by intermittent surges of sympathetic activity resulting in vasoconstriction. Because the MSNA responses to obstructive apnea are blunted during O2 administration, they appear to be linked to intermittent arterial hypoxemia and stimulation of arterial chemoreceptors.

scholarly journals 2019 Ludwig Lecture: Rhythms in sympathetic nerve activity are a key to understanding neural control of the cardiovascular system

2020 ◽  
Vol 318 (2) ◽  
pp. R191-R205 ◽  
Author(s):  
Susan M. Barman
Keyword(s):  
Brain Stem ◽  
Cardiovascular System ◽  
Sympathetic Nerve ◽  
Neural Control ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Sympathetic Nerves ◽  
Ventrolateral Medulla ◽  
Nerve Activity

This review is based on the Carl Ludwig Distinguished Lecture, presented at the 2019 Experimental Biology Meeting in Orlando, FL, and provides a snapshot of >40 years of work done in collaboration with the late Gerard L. Gebber and colleagues to highlight the importance of considering the rhythmic properties of sympathetic nerve activity (SNA) and brain stem neurons when studying the neural control of autonomic regulation. After first providing some basic information about rhythms, I describe the patterns and potential functions of rhythmic activity recorded from sympathetic nerves under various physiological conditions. I review the evidence that these rhythms reflect the properties of central sympathetic neural networks that include neurons in the caudal medullary raphe, caudal ventrolateral medulla, caudal ventrolateral pons, medullary lateral tegmental field, rostral dorsolateral pons, and rostral ventrolateral medulla. The role of these brain stem areas in mediating steady-state and reflex-induced changes in SNA and blood pressure is discussed. Despite the common appearance of rhythms in SNA, these oscillatory characteristics are often ignored; instead, it is common to simply quantify changes in the amount of SNA to make conclusions about the function of the sympathetic nervous system in mediating responses to a variety of stimuli. This review summarizes work that highlights the need to include an assessment of the changes in the frequency components of SNA in evaluating the cardiovascular responses to various manipulations as well as in determining the role of different brain regions in the neural control of the cardiovascular system.

Cannabinoid and GABA modulation of sympathetic nerve activity and blood pressure in the dorsal periaqueductal gray of the rat

2011 ◽  
Vol 301 (6) ◽  
pp. R1765-R1772 ◽  
Author(s):  
C. Dean
Keyword(s):  
Blood Pressure ◽  
Gabaa Receptor ◽  
Defense Response ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Acute Stress ◽  
Pressor Response ◽  
Periaqueductal Gray ◽  
Nerve Activity ◽  
Gabaergic Neurotransmission

Sympathoexcitation and increased blood pressure evoked by central networks integrating defensive behavior are fundamental to the acute stress response. A balance between excitatory glutamatergic and inhibitory GABAergic neurotransmission in the dorsal periaqueductal gray (dPAG) results in a tonic level of activity in the alerting system. Neuromodulators such as endocannabinoids have been shown to influence the sympathoexcitatory and pressor components of acute stress in the dPAG, exemplified by the defense response as a model, but the mechanism of integration remains unknown. The present study examines the role of GABA and its interaction with endocannabinoids in modulating sympathetic nerve activity and blood pressure related to the defense response. Microinjection of the broad-spectrum excitatory amino acid dl-homocysteic acid (DLH) identified sites of the defense pathway in the dPAG from which an increase in renal sympathetic nerve activity and blood pressure could be evoked, and subsequent microinjections were made at the same site through a multibarrelled micropipette. Blockade of GABAA receptors or microinjection of the cannabinoid 1 receptor agonist anandamide elicited a renal sympathoexcitation and pressor response. Prior microinjection of the GABAA receptor antagonist gabazine attenuated the sympathoexcitation and pressor response associated with anandamide microinjection. In contrast, the sympathetic response to DLH was enhanced by GABAA receptor blockade. These data demonstrate that sympathoexcitatory neurons in the dPAG are under tonic inhibition by GABA and that endocannabinoids modulate this GABAergic neurotransmission to help regulate components of the defense response.

Hypothalamic and cortical sympathetic responses relay in the medulla of the rat

1992 ◽  
Vol 263 (3) ◽  
pp. R544-R552 ◽  
Author(s):  
D. F. Cechetto ◽  
S. J. Chen
Keyword(s):  
Spinal Cord ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Thoracic Spinal Cord ◽  
Efferent Pathway ◽  
Arterial Blood ◽  
Sympathetic Responses ◽  
Stimulation Of

Previously, investigations have indicated that the efferent pathway for sympathetic responses originating in the insular cortex (IC) must initially synapse in the lateral hypothalamic area (LHA). The LHA projects to both the ventrolateral medulla (VLM) and directly to the thoracic spinal cord. To determine the role of the VLM in mediating sympathetic responses from the IC and the LHA, in alpha-chloralose-anesthetized rats, renal nerve responses were recorded following electrical stimulation of these two forebrain sites before and after bilateral injection (300 nl) of cobalt (a synaptic blocking agent) into the VLM. The results demonstrated that a complete block of the increase in sympathetic nerve activity following stimulation of the IC or the LHA could be obtained with cobalt injections into the VLM. The most effective injection sites were located in the rostral ventrolateral medulla at the rostrocaudal middle and posterior regions of the C1 group of neurons. Chemical stimulation with DL-homocysteic acid, in the LHA, to activate cell bodies only evoked a decrease in arterial blood pressure and sympathetic nerve activity. These responses were also blocked by cobalt injection into the VLM. Injections of cobalt into the nucleus of the solitary tract did not block sympathetic responses elicited from the LHA. These results indicate that the efferent pathway for sympathetic responses from the IC through the LHA goes to the preganglionic region of the spinal cord via a mandatory synapse in the VLM.

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