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

Dietrich, Péter; Moleda, Lukas; Kees, Frieder; Muller, Matthew D.; Straub, Rainer H.; Hellerbrand, Claus; Wiest, Reiner

doi:10.1016/j.jhep.2012.09.027

Cited by 23 publications

(24 citation statements)

References 47 publications

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“…These animals exhibited mesenteric sympathetic nerve atrophy/regression, but administration of agents that inhibit these nerve disorders (e.g., capsaicin [114] and gambogic amide [115]) ameliorated the hyperdynamic circulatory syndrome. These impaired neuronal functions were also associated with decreased release of neuropeptide Y, a neurotransmitter and potent vasoconstrictor produced by the sympathetic nervous system [116]. Administration of exogenous neuropeptide Y decreased excessive vasodilation of mesenteric arteries of portal hypertensive rats, indicating that hypocontractility of mesenteric arteries is at least in part mediated by an impaired production of neural factors [116,117].…”

Section: The Mesenteric Vasculature In Portal Hypertensionmentioning

confidence: 97%

“…These impaired neuronal functions were also associated with decreased release of neuropeptide Y, a neurotransmitter and potent vasoconstrictor produced by the sympathetic nervous system [116]. Administration of exogenous neuropeptide Y decreased excessive vasodilation of mesenteric arteries of portal hypertensive rats, indicating that hypocontractility of mesenteric arteries is at least in part mediated by an impaired production of neural factors [116,117].…”

Section: The Mesenteric Vasculature In Portal Hypertensionmentioning

confidence: 97%

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Biology of portal hypertension

McConnell

Iwakiri

2017

Hepatol Int

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Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

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Section: The Mesenteric Vasculature In Portal Hypertensionmentioning

confidence: 97%

Section: The Mesenteric Vasculature In Portal Hypertensionmentioning

confidence: 97%

Biology of portal hypertension

McConnell

Iwakiri

2017

Hepatol Int

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“…Alterations in the production and function of neuropeptides are also involved in the pathogenesis of PHT. Indeed, the reactivity to the adrenergic vasoconstrictor neurotransmitter noradrenaline is altered due both to down‐regulation of proteins implicated in adrenergic neurotransmission, including neuropeptide Y, and to mesenteric sympathetic nerve atrophy . There are also disturbances in the nonadrenergic, noncholinergic perivascular innervation system in the mesenteric vascular bed during PHT, with NO overproduction from neuronal NOS in perivascular nitrergic nerves, which participate in the development of splanchnic hyperdynamic circulation in PHT.…”

Section: Molecular Components Of Splanchnic Vasodilatationmentioning

confidence: 99%

Molecular pathophysiology of portal hypertension

2015

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Over the past two decades the advances in molecular cell biology have led to significant discoveries about the pathophysiology of portal hypertension (PHT). In particular, great progress has been made in the study of the molecular and cellular mechanisms that regulate the increased intrahepatic vascular resistance (IHVR) in cirrhosis. We now know that the increased IHVR is not irreversible, but that both the structural component caused by fibrosis and the active component caused by hepatic sinusoidal constriction can be, at least partially, reversed. Indeed, it is now apparent that the activation of perisinusoidal hepatic stellate cells, which is a key event mediating the augmented IHVR, is regulated by multiple signal transduction pathways that could be potential therapeutic targets for PHT treatment. Furthermore, the complexity of the molecular physiology of PHT can also be appreciated when one considers the complex signals capable of inducing vasodilatation and hyporesponsiveness to vasoconstrictors in the splanchnic vascular bed, with several vasoactive molecules, controlled at multiple levels, working together to mediate these circulatory abnormalities. Added to the complexity is the occurrence of pathological angiogenesis during the course of disease progression, with recent emphasis given to understanding its molecular machinery and regulation. Although much remains to be learned, with the current availability of reagents and new technologies and the exchange of concepts and data among investigators, our knowledge of the molecular basis of PHT will doubtless continue to grow, accelerating the transfer of knowledge generated by basic research to clinical practice. This will hopefully permit a better future for patients with PHT. (HEPATOLOGY 2015;61:1406-1415 Pathophysiology of Portal HypertensionPortal hypertension (PHT) is a major complication of chronic liver diseases, including cirrhosis of the liver, which are leading causes of death and liver transplantation worldwide. 1,2 The prime determinant of PHT in cirrhosis is the increased intrahepatic vascular resistance (IHVR) that occurs in the cirrhotic liver, which manifests through distortion of the liver vascular architecture caused by fibrosis, scarring, and nodule formation, as well as by hepatic sinusoidal cellular alterations that promote constriction of the hepatic sinusoids. Another further mechanism determining PHT is an increased splanchnic blood flow, partly due to mesenteric arteriolar vasodilatation and decreased vascular responsiveness to endogenous vasoconstrictors. This increased splanchnic blood flow perpetuates and exacerbates portal pressure elevation, promotes ascites and spontaneous bacterial peritonitis, and is associated with the formation of portosystemic collateral vessels and esophageal varices, which are, in turn, responsible for life-threatening consequences like gastroesophageal bleeding, portosystemic encephalopathy, and sepsis. 3 A growing body of evidence indicates that angiogenesis, the formation of new blood vessels from...

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“…In portal hypertension, the downregulation of neuropeptide Y, involved in adrenergic neurotransmission, causes a reduction in reactivity to noradrenaline [74]. In cirrhosis, the increased systemic levels of norepinephrine may induce the presynaptic α 2 -adrenergic inhibition of neuropeptide Y production [75].…”

Section: Impaired Reactivity To Circulating Vasoconstrictorsmentioning

confidence: 99%

Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis

et al. 2017

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In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic vascular resistance and portal blood flow. Significant vasodilation in the arterial splanchnic district is crucial for an increase in portal flow. In this pathological condition, increased levels of circulating endogenous vasodilators, including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids, glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular response to vasoconstrictors are the main mechanisms underlying splanchnic vasodilation. In this review, the molecular pathways leading to splanchnic vasodilation will be discussed in detail.

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

Cited by 23 publications

References 47 publications

Biology of portal hypertension

Biology of portal hypertension

Molecular pathophysiology of portal hypertension

Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis

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