Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

Cheyuo, Cletus; Jacob, Asha; Wang, Haichao

doi:10.1152/ajpendo.00508.2011

Cited by 33 publications

(33 citation statements)

References 97 publications

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“…One important exception is ghrelin, the only orexigenic peptide hormone so far described. Ghrelin interacts with the brain reward pathways to increase food intake, alter food preference and enhance food reward, thus influencing hedonic feeding control [32,33].…”

Section: Ghrelin An Addiction Hormonementioning

confidence: 99%

The Ghrelin System; Beyond the Role in Energy Homeostasis

Šaranac

Gucev

2017

FU Med Biol

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Section: Ghrelin An Addiction Hormonementioning

confidence: 99%

The Ghrelin System; Beyond the Role in Energy Homeostasis

Šaranac

Gucev

2017

FU Med Biol

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“…Although this study investigated the differential effects of indomethacin on renal and cardiac SNA in sepsis, the effects on other sympathetic nerves, such as those innervating muscle, gut, and spleen, remain to be determined. It also remains to be determined whether selectively reducing the increase in CSNA early in sepsis is associated with improved outcome in hyperdynamic sepsis; however, this is supported by the finding that central sympatholytics and ␤-blockers have beneficial effects in human and experimental sepsis (1,6,13,19,33).…”

Section: Perspectives and Significancementioning

confidence: 99%

“…These changes are accompanied by activation of the sympathetic nervous system, as demonstrated by increased circulating levels of plasma catecholamines in septic humans (12), increased renal sympathetic nerve activity (RSNA) in endotoxemic rats (22,30), and increased SNA to the heart and kidneys in sheep with hyperdynamic sepsis (24). It would be expected that an increase in SNA would be beneficial in sepsis, for example, by maintaining arterial pressure; however there is recent evidence that sympatholytic agents have beneficial actions in experimental sepsis in rodents (1,6,13,33). It is, therefore important to identify the mechanisms leading to the organ-selective increase in SNA in sepsis, as this may lead to development of more targeted treatments.…”

mentioning

confidence: 99%

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

Booth

Ramchandra

Calzavacca

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Booth LC, Ramchandra R, Calzavacca P, May CN. Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis. Am J Physiol Regul Integr Comp Physiol 307: R75-R81, 2014. First published April 30, 2014 doi:10.1152/ajpregu.00450.2013.-Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg Ϫ1 ·min Ϫ1 ) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA.sepsis; cardiac sympathetic nerve activity; renal sympathetic nerve activity; PGE2; indomethacin; baroreflex curve; sheep SEPSIS AND SEPTIC SHOCK ARE the chief causes of death in intensive care units with mortality rates of between 30 and 70% when combined with multiorgan failure (2, 20, 21, 28). Although the incidence of sepsis is increasing, our knowledge of the pathology is limited, and current treatments, including volume resuscitation and vasoconstrictors, are only marginally effective. In human septic patients the most common hemodynamic profile is a hyperdynamic circulation, characterized by peripheral vasodilatation and hypotension accompanied by an increased cardiac output (16,17). These changes are accompanied by activation of the sympathetic nervous system, as demonstrated by increased circulating levels of plasma catecholamines in septic humans (12), increased renal sympathetic nerve activity (RSNA) in endotoxemic rats (22,30), and increased SNA to the heart and kidneys in sheep with hyperdynamic sepsis (24). It would be expected that an increase in SNA would be beneficial in sepsis, for example, by maintaining arterial pressure; however there...

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“…However, it is important to consider that capsaicin would initially activate TRPV1 but then desensitize the neuronal fibres, leading to a loss of signalling mediated by TRPV1 and many other neuronal receptors, which may have distinct roles in the response to sepsis. These would include other TRP channels (Almeida et al ., ; Konno et al ., ), neuropeptides (Beer et al ., ; Westphal et al ., ; Neunaber et al ., ), ghrelin (Cheyuo et al ., ) and NO (Berg et al ., ), amongst others. Subsequently, the protective role of TRPV1 in sepsis was confirmed in experiments using TRPV1KO mice.…”

Section: Trpv1 and Its Role In Sepsismentioning

confidence: 99%

TRPV1 and SP: key elements for sepsis outcome?

Bodkin

Fernandes²

2013

British J Pharmacology

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Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depends on the severity of systemic inflammation, which can be directly influenced by several factors, including the immune response of the patient. Currently, there is a lack of effective drugs to treat sepsis, and thus there is a need to develop new drugs to improve sepsis outcome. Several mediators involved in the formation of sepsis have now been identified, but the mechanisms underlying the pathology remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) receptor and the neuropeptide substance P (SP) have recently been demonstrated as important targets for sepsis and are located on sensory neurones and non-neuronal cells. Herein, we highlight and review the importance of sensory neurones for the modulation of sepsis, with specific focus on recent findings relating to TRPV1 and SP, with their distinct abilities to alter the transition from local to systemic inflammation and also modify the overall sepsis outcome. We also emphasize the protective role of TRPV1 in this context. LINKED ARTICLESThis article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx

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Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

Cited by 33 publications

References 97 publications

The Ghrelin System; Beyond the Role in Energy Homeostasis

The Ghrelin System; Beyond the Role in Energy Homeostasis

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

TRPV1 and SP: key elements for sepsis outcome?

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