Activation of Spinobulbar Lamina I Neurons by Static Muscle Contraction

Wilson, L. B.; Andrew, David P.; Craig, A. D.

doi:10.1152/jn.00609.2001

Cited by 60 publications

(43 citation statements)

References 20 publications

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“…In hypertension, combined or individual activation of either the mechanical (i.e., mechanoreflex) or metabolic component (i.e., metaboreflex) of the EPR results in a heightened sympathetically mediated cardiovascular response (2,13,22,23,34,38). To date, however, the mechanisms underlying EPR overactivity in hypertension remain largely unknown.The nucleus tractus solitarius (NTS) within the medulla oblongata of the brainstem is a central site of integration for sensory information from skeletal muscle afferents fibers (7,26,42). As evidence, anterograde tracing with biotinylated dextran amine of ascending neuronal projections from the spinal cord, to which skeletal muscle afferents contribute, has demonstrated that these fibers project to the NTS (30).…”

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confidence: 99%

“…The nucleus tractus solitarius (NTS) within the medulla oblongata of the brainstem is a central site of integration for sensory information from skeletal muscle afferents fibers (7,26,42). As evidence, anterograde tracing with biotinylated dextran amine of ascending neuronal projections from the spinal cord, to which skeletal muscle afferents contribute, has demonstrated that these fibers project to the NTS (30).…”

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confidence: 99%

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Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

Murphy

Mizuno²,

Downey

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Murphy MN, Mizuno M, Downey RM, Squiers JJ, Squiers KE, Smith SA. Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats. Am J Physiol Heart Circ Physiol 304: H1547-H1557, 2013. First published April 5, 2013; doi:10.1152/ajpheart.00235.2012.-The functions of the skeletal muscle exercise pressor reflex (EPR) and its mechanically sensitive component are augmented in hypertension producing exaggerated increases in blood pressure during exercise. Afferent information from the EPR is processed in the nucleus tractus solitarius (NTS). Within the NT, nitric oxide (NO), produced via L-arginine oxidation by neuronal nitric oxide synthase (nNOS), buffers the pressor response to EPR activation. Therefore, EPR overactivity may manifest as a decrease in NO production due to reductions in nNOS. We hypothesized that nNOS protein expression is lower in the NTS of spontaneously hypertensive (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. Further, we examined whether nNOS is expressed with FOS, a marker of neuronal excitation induced by EPR activation. The EPR and mechanoreflex were intermittently activated for 1 h via hindlimb static contraction or stretch, respectively. These maneuvers produced significantly greater pressor responses in SHR during the first 25 min of stimulation. Within the NTS, nNOS expression was lower from Ϫ14.9 to Ϫ13.4 bregma in SHR compared with WKY. For example, at Ϫ14.5 bregma the number of NTS nNOS-positive cells in SHR (13 Ϯ 1) was significantly less than WKY (23 Ϯ 2). However, the number of FOS-positive cells after muscle contraction in this area was not different (WKY ϭ 82 Ϯ 18; SHR ϭ 75 Ϯ 8). In both groups, FOS-expressing neurons were located within the same areas of the NTS as neurons containing nNOS. These findings demonstrate that nNOS protein expression is lower within NTS areas excited by skeletal muscle reflexes in hypertensive rats.hypertension; exercise; nucleus tractus solitarius PHYSICAL ACTIVITY INDUCES increases in arterial blood pressure (ABP), heart rate (HR), and sympathetic nerve activity (20,32). In hypertension, exercise evokes abnormally exaggerated elevations in each of these variables (2, 9, 27). This places hypertensive patients at a greater risk for the occurrence of an adverse cardiovascular and/or cerebrovascular event during or immediately after a bout of exercise (6, 21). As a result, the intensity and duration of exercise prescription at a level that is both safe and therapeutically effective are often limited. Thus determining the cause of the cardiovascular hyperexcitability manifest in hypertension is clinically important.Exercise-induced autonomic changes in the cardiovascular system are mediated by the central command, the arterial baroreflex and the exercise pressor reflex (EPR; Refs. 4,18,19). Of these, recent evidence in both the animal and human literature suggests that the EPR contributes significantly to the abnormally accentuated circulatory response to ...

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confidence: 99%

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confidence: 99%

Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

Murphy

Mizuno²,

Downey

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Future studies should verify whether this 5-HT 1A Rgated lumbar spinoparabrachial respiratory-inhibiting pathway is glutamatergic (impinging on a respiratory-inhibiting network in LPBN-KFN) or GABAergic/glycinergic (impinging on a respiratory-exciting network). In addition, somatic afferents (e.g., those from skeletal muscles) may also be relayed by spinal lamina I neurons directly to the medullary respiratory circuits (Wilson et al 2002). Whether this pathway is also subject to 5-HT 1A Rgating remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

A latent serotonin-1A receptor-gated spinal afferent pathway inhibiting breathing

2015

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Spinal afferents such as nociceptive afferents and group III-IV muscle afferents are known to exert an acute excitatory effect on breathing when activated. Here, we report the surprising existence of latent spinal afferents which exerted tonic inhibitory influence on breathing subliminally in anesthetized rats, an effect which was reversed upon activation of serotonin-1A receptors (5-HT 1A Rs) in lumbar spinal cord, lesion of pontine lateral parabrachial nucleus or suppression of the adjacent Kölli-ker-Fuse nucleus with NMDA receptor blockade. Smallinterfering RNA knockdown of 5-HT 1A Rs in lumbar spinal cord unequivocally localized the site of 5-HT 1A R-mediated gating of these respiratory-inhibiting interoceptive afferents to relay neurons in the spinal superficial dorsal horn at the lumbar level and not cervical spinal or supraspinal levels. Our results reveal a novel somatosensory/viscerosensory mechanism which exerts tonic inhibitory influence on homeostatic regulation of breathing independent from the classical chemoreflex excitatory pathways, and suggest a hitherto unrecognized therapeutic target in spinal dorsal horn for 5-HT 1A R-based treatment of a variety of respiratory abnormalities.

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“…Previous studies (4, 5) using electrophysiological methods have also shown that neurons in the superficial and deep dorsal horn at the L7 level are excited during muscle contraction. Furthermore, it has recently been shown that the lamina I neurons of the dorsal horn that project to the caudal ventrolateral medulla are activated by static muscle contraction (40). In addition, the codistribution of c-Fos neurons and NOS-positive staining in this region of the superficial horn was determined by a double-label method and provided a unique opportunity to determine the neurochemical characteristics of activated neurons.…”

Section: Discussionmentioning

confidence: 99%

Role of NO in modulating neuronal activity in superficial dorsal horn of spinal cord during exercise pressor reflex

Mitchell

2002

American Journal of Physiology-Heart and Circulatory Physiology

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Li, Jianhua, and Jere H. Mitchell. Role of NO in modulating neuronal activity in superficial dorsal horn of spinal cord during exercise pressor reflex. Am J Physiol Heart Circ Physiol 283: H1012-H1018, 2002. First published May 23, 2002 10.1152/ajpheart.00174.2002-Static contraction of hindlimb skeletal muscle in cats induces a reflex pressor response. The superficial dorsal horn of the spinal cord is the major site of the first synapse of this reflex. In this study, static contraction of the triceps surae muscle was evoked by electrical stimulation of the tibial nerve for 2 min in anesthetized cats (stimulus parameters: two times motor threshold at 30 Hz, 0.025-ms duration). Ten stimulations were performed and 1-min rest was allowed between stimulations. Muscle contraction caused a maximal increase of 32 Ϯ 5 mmHg in mean arterial pressure (MAP), which was obtained from the first three contractions. Activated neurons in the superficial dorsal horn were identified by c-Fos protein. Distinct c-Fos expression was present in the L6-S1 level of the superficial dorsal horn ipsilateral to the contracting leg (88 Ϯ 14 labeled cells per section at L7), whereas only scattered c-Fos expression was observed in the contralateral superficial dorsal horn (9 Ϯ 2 labeled cells per section, P Ͻ 0.05 compared with ipsilateral section). A few c-Fos-labeled cells were found in control animals (12 Ϯ 5 labeled cells per section, P Ͻ 0.05 compared with stimulated cats). Furthermore, doublelabeling methods demonstrated that c-Fos protein coexisted with nitric oxide (NO) synthase (NOS) positive staining in the superficial dorsal horn. Finally, an intrathecal injection of an inhibitor of NOS, N-nitro-L-arginine methyl ester (5 mM), resulted in fewer c-Fos-labeled cells (58 Ϯ 12 labeled cells per section) and a reduced maximal MAP response (20 Ϯ 3 mmHg, P Ͻ 0.05). These results suggest that the exercise pressor reflex induced by static contraction is mediated by activation of neurons in the superficial dorsal horn and that formation of NO in this region is involved in modulating the activated neurons and the pressor response to contraction. c-Fos expression; nitric oxide; static muscle contraction; blood pressure STATIC CONTRACTION OF HINDLIMB skeletal muscle evokes increases in arterial blood pressure and heart rate, referred to as the "exercise pressor reflex" (26,30). It has been shown that the reflex cardiovascular responses to static muscle contraction are mediated by both group III (thinly myelinated A␦) and group IV (unmyelinated C) fibers (25, 26). It has been reported (19, 30) that neural signals from contracting skeletal muscle are generated by activating mechanically and metabolically sensitive nerve ending (receptors) located in the skeletal muscle. These neural signals are subsequently carried to the central nervous system by group III and group IV afferent fibers (3, 26). The majority of group III and group IV skeletal muscle afferent fibers make their first synapse in the superficial dorsal horn of the spinal cord (24,29). ...

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Activation of Spinobulbar Lamina I Neurons by Static Muscle Contraction

Cited by 60 publications

References 20 publications

Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

A latent serotonin-1A receptor-gated spinal afferent pathway inhibiting breathing

Role of NO in modulating neuronal activity in superficial dorsal horn of spinal cord during exercise pressor reflex

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