Rostral ventrolateral medullary opioid receptor activation  modulates pressor response to muscle contraction

Caringi, Daryl; Mokler, David J.; Koester, David; Ally, Ahmmed

doi:10.1152/ajpheart.1998.274.1.h139

Cited by 14 publications

(15 citation statements)

References 27 publications

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“…For example, microinjection of opioid agonists into the rVLM produces profound hypotension (47) and decreases in BP and HR in normotensive, chronic stressinduced hypertensive and spontaneously hypertensive rats, whereas naloxone injected into the rVLM blocks these responses. Furthermore, injection of opioid agonists into the rVLM inhibits BP responses to carotid occlusion and muscular exercise (8,31,47). These studies suggest that opioids in the rVLM have the potential to inhibit premotor sympathetic cardiovascular outflow.…”

Section: Discussionmentioning

confidence: 80%

“…Opioid neurotransmitters in the rVLM are capable of regulating sympathetic outflow and, ultimately, cardiovascular function (8,44,47). For example, microinjection of opioid agonists into the rVLM produces profound hypotension (47) and decreases in BP and HR in normotensive, chronic stressinduced hypertensive and spontaneously hypertensive rats, whereas naloxone injected into the rVLM blocks these responses.…”

Section: Discussionmentioning

confidence: 99%

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Role of glutamate in the rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation

Zhou

Fu²,

Guo³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Visceral sympathoexcitatory reflexes induced by stimulation of the gallbladder with bradykinin (BK) are attenuated by electroacupuncture (EA) at Neiguan-Jianshi (P5-6) acupoints located over the median nerve. Previous studies have shown that neurons in the rostral ventrolateral medulla (rVLM) receive convergent input from visceral organs and somatic nerves (activated by EA). Glutamate (Glu), an important excitatory neurotransmitter in the rVLM, processes visceral sympathoexcitatory cardiovascular reflexes. In the present study, we determined the relation between EA-mediated opioidergic modulation of visceral cardiovascular responses and Glu. Reflex cardiovascular responses were evoked by application of BK to the gallbladder before and after EA in anesthetized cats. Glu concentrations ([Glu]) were measured by HPLC from samples collected by microdialysis probe(s) inserted unilaterally or bilaterally into the rVLM. BK-induced reflex responses and [Glu] were attenuated by 45% and 70%, respectively, after 30 min of EA (n = 6). EA alone did not change [Glu] in the rVLM (n = 6, P > 0.05). However, microdialysis of naloxone (100 mM) into the rVLM reversed EA-related inhibition of blood pressure and [Glu] (n = 5). Immunohistochemical visualization showed that delta-opioid receptors colocalized with, and were in close apposition to, vesicular Glu transporter 3- and c-Fos-double-labeled perikarya and processes of rVLM neurons after gallbladder stimulation with BK. These data suggest that EA attenuates BK-induced visceral sympathoexcitatory reflexes through opioid-mediated inhibition of Glu's action in the rVLM.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Role of glutamate in the rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation

Zhou

Fu²,

Guo³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…A migration of fentanyl sufficient to reach the brainstem would certainly negate the significance of our findings because the direct effect of fentanyl on medullary opioid receptors is recognized to affect neurons involved in cardiovascular (Sun et al . 1996; Caringi et al . 1998) and ventilatory (Lalley, 2008) control.…”

Section: Discussionmentioning

confidence: 99%

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

Amann

Runnels

Morgan

et al. 2011

The Journal of Physiology

143

158

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Non-technical summary We investigated the role of thin fibre muscle afferents in the circulatory response to exercise in humans. The results not only document the importance of continuous afferent feedback from working human skeletal muscle to achieve appropriate haemodynamic and ventilatory responses to exercise but also suggest that the relative contribution of this mechanism is larger than traditionally accepted. AbstractWe investigated the role of skeletal muscle afferent feedback in circulatory control during rhythmic exercise in humans. Nine healthy males performed single leg knee-extensor exercise (15/30/45 watts, 3 min each) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. Cardiac output and femoral blood flow were determined, and femoral arterial/venous blood samples were collected during the final minute of each workload. To rule out cephalad migration of fentanyl to the brainstem, we documented unchanged resting ventilatory responses to different levels of hypercapnia. There were no haemodynamic differences between conditions at rest. However, during exercise cardiac output was ∼20% lower with fentanyl blockade compared to control (P < 0.05), secondary to a 6% and 13% reduction in heart rate and stroke volume, respectively. Throughout exercise mean arterial pressure (MAP) was reduced by 7% (P < 0.01) which is likely to have contributed to the 15% fall in femoral blood flow. However, MAP was not completely responsible for this peripheral haemodynamic change as vascular conductance was also attenuated (∼9%). Evidence of increasing noradrenaline spillover (P = 0.09) implicated an elevation in sympathetic outflow in this response. The attenuated femoral blood flow during exercise with fentanyl was associated with a 17% reduction in leg O 2 delivery (P < 0.01) and a concomitant rise in the arteriovenous O 2 difference (4-9%), but leg O 2 consumption remained 7-13% lower than control (P < 0.05). Our findings reveal an essential contribution of continuous muscle afferent feedback to ensure the appropriate haemodynamic and ultimately metabolic response to rhythmic exercise in humans. Abbreviations FBF, femoral blood flow; HR, heart rate; LVC, leg vascular conductance; MAP, mean arterial pressure; NA, noradrenaline; SV, stroke volume.

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“…Indeed, two studies have suggested a tonically active, inhibitory input to the CVL (Badoer and Chalmers, 1992) and the RVL (Sun et al, 1996). However, a recent study investigating the modulation by opioids of the cardiovascular responses to static muscle contraction has shown that microdialysis of NAL into the CVL or the RVL did not alter baseline mean arterial pressure or heart rate (Caringi et al, 1998). Our results showing a significant increase in Fos-LI in the RVL, thus, are in good agreement with the finding that NAL alone increases blood pressure and heart rate when injected into the RVL in normal rats (Sun et al, 1996).…”

Section: Is There a Tonic Opioid Control Of Cardiorespiratory Functions?mentioning

confidence: 99%

Is there tonic activity in the endogenous opioid systems? A c-Fos study in the rat central nervous system after intravenous injection of naloxone or naloxone-methiodide

2000

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This study examined the possibility that a tonic activity in the endogenous opioid systems (EO systems) exists in animals under normal conditions. In a first set of experiments, concurrent changes in behavioral responses and in the numbers of c-Fos-like immunoreactive (Fos-LI) neurons in 58 structures of the brain and lumbosacral spinal cord were analyzed in rats after systemic administration of the opioid antagonist naloxone (NAL; 2 mg/kg). Possible roles of the EO systems were inferred from changes in the numbers of Fos-LI neurons between normal rats that received either NAL or the same volume of saline. Free-floating sections were processed immunohistochemically for c-Fos protein using standard avidin-biotin complex methods. After NAL, the numbers of Fos-LI neurons were significantly increased in the area postrema; in the caudal, intermediate, and rostral parts of the nucleus tractus solitarii; in the rostral ventrolateral medulla; in the Kölliker-Fuse nucleus; in the supramammillary nucleus; and in the central nucleus of the amygdala. In a second set of experiments examining changes in c-Fos expression in the latter structures, similar increases were found after NAL but not after an equimolar dose of NAL-methiodide, a preferential, peripherally acting opioid receptor antagonist. Therefore, Fos-LI was likely triggered after blockade of central opioid receptors, but not peripheral opioid receptors, releasing neurons from EO system-mediated inhibition. The results of this study suggest the existence of a tonic activity of the EO systems exerted on a restricted number of brain regions in normal rats. This tonic activity of the EO systems may control part of the neural networks involved in cardiorespiratory functions and in emotional and learning processes.

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Rostral ventrolateral medullary opioid receptor activation modulates pressor response to muscle contraction

Cited by 14 publications

References 27 publications

Role of glutamate in the rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation

Role of glutamate in the rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

Is there tonic activity in the endogenous opioid systems? A c-Fos study in the rat central nervous system after intravenous injection of naloxone or naloxone-methiodide

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