Blockage of the afferent sensitive pathway prevents sympathetic atrophy and hemodynamic alterations in rat portal hypertension

Ezkurdia, Nahia; Coll, Mar; Raurell, Imma; Rodriguez, Sonia; Cuenca, Silvia; González, Antonio; Guàrdia, J; Esteban, Rafael; Genescà, Joan; Martell, Marı́a

doi:10.1111/j.1478-3231.2012.02762.x

Cited by 14 publications

(21 citation statements)

References 33 publications

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“…6 G and H) and p75 neurotrophin receptor (i.e., reduced neurite sprouting) in DH laminae I-III (Fig. 6 K and L), both of which are largely dependent on neuronal activity (43). Likewise, HUP-A-mediated postsynaptic inhibition (44) may be responsible for the observed down-regulation of the CRLR and the NK1R in DH sensory neurons (Fig.…”

Section: Discussionmentioning

confidence: 93%

Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A

Thakor

Han

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Neuropathic pain, one of the most debilitating sequelae of neurotrauma, is an unmet clinical need for at least 40% of patients with spinal cord injury (SCI). We demonstrate that [-]-huperzine A (HUP-A), a naturally occurring Lycopodium alkaloid isolated from the Chinese club moss, Huperzia serrata , with potent reversible inhibitory action on acetylcholinesterase and N -methyl- D -aspartate glutamate receptors, offers an exceptional prospect for multimodal treatment of SCI-induced neuropathic pain in rats. HUP-A restores homeostasis of central sensory neurocircuitry without invoking drug tolerance and dependence or respiratory suppression. We therefore conclude that multimodal actions provide a fresh translational approach to reduce chronic pain.

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Section: Discussionmentioning

confidence: 93%

Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A

Thakor

Han

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…However, recent reports suggest splanchnic sympathetic atrophy in portal hypertension. In detail, marked reduction of sympathetic nerves and decreased protein expression of tyrosine-hydroxylase key enzyme for NA synthesis have been demonstrated in portal hypertensive mesenteric arteries [10][11][12]. Applying a model of repetitive electric PNS resembling sustained splanchnic vascular SNS activity, we report that cirrhotic rats display almost doubled and about 30% increased NA release caused by first and subsequent PNS, respectively.…”

Section: Discussionmentioning

confidence: 93%

“…Es gibt deutliche Evidenz dafür, dass bei portaler Hypertension die systemischen NA-Plasmakonzentrationen hauptsächlich von der mesenterialen NA-Produktion abhängen [5]. Aber anders als bei systemischen NAKonzentrationen sind Daten zu lokaler splanchnischer Neurotransmitter-Produktion und -Sekretion sehr spärlich vorhanden und zudem kontrovers [6][7][8][9][10][11][12].…”

Section: Dysbalance In Sympathetic Neurotransmitter Release and Actiounclassified

“…In case of portal hypertension, systemic plasma NA levels could mainly depend on splanchnic NA production [5]. Besides systemic NA levels, data in terms of actual splanchnic synthesis/release of neurotransmitters are scarce and controversial [6][7][8][9][10][11][12]. Neuropeptide Y (NPY) is co-stored and co-released with NA from secretory vesicles of sympathetic nerve terminals, inducing potentiation of a 1 -adrenergic vasoconstriction via G-proteinassociated postsynaptic Y 1 receptors [13].…”

Section: Introductionmentioning

confidence: 99%

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Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dietrich¹,

Moleda²,

Kees

et al. 2013

Journal of Hepatology

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“…It has also been proposed that during portal hypertension, pressure changes detected at portal level could be the afferent sensory signal triggering this hemodynamic response [5]. We have demonstrated that blockade of sensory afferent nerves in portal hypertensive rats, simultaneously prevents c-fos activation in cardiovascular regulatory nuclei of the brain, hemodynamic alterations and sympathetic atrophy of nerves innervating the superior mesenteric artery (SMA) [6]–[8].…”

Section: Introductionmentioning

confidence: 92%

Inhibition of Neuronal Apoptosis and Axonal Regression Ameliorates Sympathetic Atrophy and Hemodynamic Alterations in Portal Hypertensive Rats

et al. 2014

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Background and AimA neuronal pathway participates in the development of portal hypertension: blockade of afferent sensory nerves in portal vein ligated (PVL) rats simultaneously prevents brain cardiovascular regularory nuclei activation, neuromodulator overexpression in superior mesenteric ganglia, sympathetic atrophy of mesenteric innervation and hemodynamic alterations. Here we investigated in PVL rats alterations in neuromodulators and signaling pathways leading to axonal regression or apoptosis in the superior mesenteric ganglia and tested the effects of the stimulation of neuronal proliferation/survival by using a tyrosine kinase receptor A agonist, gambogic amide.ResultsThe neuronal pathway was confirmed by an increased neuronal afferent activity at the vagal nodose ganglia and the presence of semaphorin3A in sympathetic pre-ganglionic neurons at the intermediolateral nucleus of the spinal cord of PVL rats. Expression of the active form of tyrosine kinase receptor A (phosphorylated), leading to proliferation and survival signaling, showed a significant reduction in PVL comparing to sham rats. In contrast, the apoptotic and axonal retraction pathways were stimulated in PVL, demonstrated by a significant overexpression of semaphorin 3A and its receptor neuropilin1, together with increases of cleaved caspase7, inactive poly(ADP-ribose) polymerase and Rho kinase expression. Finally, the administration of gambogic amide in PVL rats showed an amelioration of hemodynamic alterations and sympathetic atrophy, through the activation of survival pathways together with the inhibition of apoptotic cascades and Rho kinase mediated axonal regression.ConclusionThe adrenergic alteration and sympathetic atrophy in mesenteric vessels during portal hypertension is caused by alterations on neuromodulation leading to post-ganglionic sympathetic regression and apoptosis and contributing to splanchnic vasodilation.

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Blockage of the afferent sensitive pathway prevents sympathetic atrophy and hemodynamic alterations in rat portal hypertension

Abstract: These results indicate that the nervous system has a central role in the genesis of the circulatory abnormalities of portal hypertension, and support that mesenteric sympathetic atrophy contributes to splanchnic arterial vasodilation.

Cited by 14 publications

References 33 publications

Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A

Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Inhibition of Neuronal Apoptosis and Axonal Regression Ameliorates Sympathetic Atrophy and Hemodynamic Alterations in Portal Hypertensive Rats

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