Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension

Coll, Mar; Genescà, Joan; Raurell, Imma; Rodríguez–Vilarrupla, Aina; Mejías, Marc; Piñeiro-Otero, Teresa; Oria, Marc; Esteban, Rafael; Guàrdia, J; Bosch, Jaime; Martell, Marı́a

doi:10.1016/j.jhep.2008.03.015

Cited by 29 publications

(42 citation statements)

References 22 publications

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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: 78%

“…Significant increases in PNS-induced NPY release were detected only in healthy rats, demonstrating a diminished ability of sympathetic nerves to release NPY in portal hypertensive splanchnic arteries. This could represent the functional correlate for reported downregulation and regression of sympathetic innervation in the mesenteric arterial tree in cirrhosis [10,11]. Besides local SNS downregulation, other potential mechanisms could explain NPY deficiency: unquestionably, systemic NA levels are increased in cirrhosis [3,[6][7][8][9].…”

Section: Discussionmentioning

confidence: 89%

“…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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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 89%

Section: Dysbalance In Sympathetic Neurotransmitter Release and Actiounclassified

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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“…Though the reduction in peripheral resistance is slow, compensatory mechanisms play a pivotal role in maintaining and further worsening the hyperdynamic circulation ( Fig. 1) [12][13][14][15][16]. Plasma volume expansion is relevant in these cirrhotic patients, even if distribution between the central and peripheral vascular areas is often not balanced [6,17].…”

Section: Hemodynamic Changes Contributing To Hyperdynamic Syndromementioning

confidence: 99%

Clinical implications of the hyperdynamic syndrome in cirrhosis

Licata

Mazzola

Ingrassia

et al. 2014

European Journal of Internal Medicine

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The hyperdynamic syndrome is a late consequence of portal hypertension in cirrhosis. The principal hemodynamic manifestations of the hyperdynamic syndrome are high cardiac output, and increased heart rate and total blood volume, accompanied by reduced total systemic vascular resistance. Pathophysiology involves a complex of humoral and neural mechanisms that can determine hemodynamic changes, and lead to hyperdynamic circulation. In this review we focus our attention on the manifestations of the hyperdynamic syndrome. Some of these are well described and directly related to portal hypertension (varices, ascites, hepatic encephalopathy, and hepatorenal syndrome), while others, such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy, are less known as clinical manifestations related to cirrhosis and, therefore, merit further investigation.

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Washington, DC, patient navigation effort seeks to improve disparities

Printz¹

2010

Cancer

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We aimed to evaluate the effects of droxidopa (an oral synthetic precursor of norepinephrine) on the hemodynamic and renal alterations of portal hypertensive rats. Sham, portal vein‐ligated (PVL), and 4‐week biliary duct‐ligated (BDL) rats received a single oral dose of droxidopa (25‐50 mg/kg) or vehicle and hemodynamic parameters were monitored for 2 hours. Two groups of BDL and cirrhotic rats induced by carbon tetrachloride (CCl4) were treated for 5 days with droxidopa (15 mg/kg, twice daily, orally); hemodynamic parameters and blood and urinary parameters were assessed. The droxidopa effect on the Rho kinase (RhoK) / protein kinase B (AKT) / endothelial nitric oxide synthase (eNOS) pathways was analyzed by western blot in superior mesenteric artery (SMA). The acute administration of droxidopa in PVL and BDL rats caused a significant and maintained increase in arterial pressure and mesenteric arterial resistance, with a significant decrease of mesenteric arterial and portal blood flow, without changing portal pressure and renal blood flow. Two‐hour diuresis greatly increased. Carbidopa (DOPA decarboxylase inhibitor) blunted all effects of droxidopa. Chronic droxidopa therapy in BDL rats produced the same beneficial hemodynamic effects observed in the acute study, did not alter liver function parameters, and caused a 50% increase in 24‐hour diuresis volume (7.4 ± 0.9 mL/100g in BDL vehicle versus 11.8 ± 2.5 mL/100g in BDL droxidopa; P = 0.01). Droxidopa‐treated rats also showed a decreased ratio of p‐eNOS/eNOS and p‐AKT/AKT and increased activity of RhoK in SMA. The same chronic treatment in CCl4 rats caused similar hemodynamic effects and produced significant increases in diuresis volume and 24‐hour natriuresis (0.08 ± 0.02 mmol/100g in CCl4 vehicle versus 0.23 ± 0.03 mmol/100g in CCl4 droxidopa; P = 0.014). Conclusion: Droxidopa might be an effective therapeutic agent for hemodynamic and renal alterations of liver cirrhosis and should be tested in cirrhosis patients. (HEPATOLOGY 2012;56:1849–1860)

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Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension

Cited by 29 publications

References 22 publications

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

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

Clinical implications of the hyperdynamic syndrome in cirrhosis

Washington, DC, patient navigation effort seeks to improve disparities

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