Increased Sympathetic Nervous Activity and the Effects of Its Inhibition with Clonidine in Alcoholic Cirrhosis

Esler, Murray; Dudley, F. J.; Jennings, Garry; Debinski, Henry; Lambert, Gavin; Jones, Penelope; Crotty, Brendan; Colman, John; Willett, Ian R.

doi:10.7326/0003-4819-116-6-446

Cited by 111 publications

(46 citation statements)

References 32 publications

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“…Although relatively few studies have evaluated this pathway in cirrhotic patients, improved renal function and lowered noradrenaline overflow from the kidney have been observed when the intrahepatic pressure is reduced in cirrhotic patients. 69,70 These observations are consistent with the notion that the hepatoportal baroreflex contributes to increased renal sympathetic nerve activity.…”

Section: Liver Cirrhosissupporting

confidence: 80%

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

Morita

Abe

2011

Hypertens Res

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The liver, well known for its role in metabolism, clearance and storage can also be regarded as a sensory organ. The liver is an ideal place to monitor the quality and quantity of absorbed substances, because portal blood delivers substances absorbed from the intestine to the liver and these substances circulate in the hepatic vasculature before substances enter the systemic circulation. Sodium (Na + )-sensitive mechanism exists in the liver; it is stimulated by the increase in Na + concentration in the portal vein, and then hepatorenal reflex is triggered. Renal sympathetic nerve activity is reflexively decreased and urinary Na + excretion is increased. This Na + -sensitive hepatorenal reflex has a significant role in post-prandial natriuresis. However, the long-term role of this reflex in Na + homeostasis may be less important, probably because of the desensitization of Na + -sensitive mechanisms. Na + -K + -2Cl -cotransporter (NKCC1) is involved in the hepatoportal Na + -sensitive mechanism, and NKCC1 expression is reduced if the hepatoportal region is exposed to high Na + concentrations for a long time. This situation occurs when animals intake a high-sodium chloride diet for a long time. Liver cirrhosis also impairs the Na + -sensitive hepatorenal reflex. Hepatoportal baroreceptor-induced renal sympathetic excitation and the impaired Na + -sensitive hepatorenal reflex may partially explain the Na + retention in liver cirrhosis. Keywords: hepatorenal reflex; hepatic afferent nerve; liver cirrhosis; post-prandial natriuresis; renal sympathetic nerve It is well documented that the mammalian liver is not only a metabolic, clearance and storage organ but also contains many receptors, including osmoreceptors, 1,2 baroreceptors 3,4 and ionic receptors. [5][6][7] Given the roles that these receptors have in the systemic circulation, it is possible that they are also involved in the regulation of body fluid homeostasis. A growing body of evidence suggests that the osmoreceptors and ionic receptors in the liver and its vasculature detect a variety of physiological events and are responsible for the activation of a number of physiological responses, which may have important roles in the regulation of body fluid homeostasis. The important features of the hepatic sensor mechanism are: (1) substances consumed orally are absorbed from the intestine into the blood, circulate in the hepatic vasculature and then enter the systemic circulation; and (2) the portal venous blood flow is 20-25% of the cardiac output. Because of these features, the hepatic osmoreceptors and ionic receptors have advantages over those receptors located in the systemic circulation. First, the hepatic receptors are triggered by changes in portal venous osmolality and ionic concentration before any changes occur in the systemic blood, and then reflexively regulate renal excretion and intestinal absorption. 7-10 Second, the concentrations of the absorbed substances in the hepatoportal region and the changes in them are 4-5 times greater than those in th...

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Section: Liver Cirrhosissupporting

confidence: 80%

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

Morita

Abe

2011

Hypertens Res

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“…Persistent cardiac sympathetic activation is present in patients with depressive illness 40 and cirrhosis, 43 where it is thought to be harmful. Cardiac sympathetic stimulation is at a high level in heart failure, 44,45 where it is known with certainty to be harmful, 19 and countered with β-adrenergic blockade.…”

Section: Potential Neural Mechanisms Of Toxicity Of the Sympathetic Pmentioning

confidence: 99%

Obesity Paradox in Hypertension

et al. 2018

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“…Some supportive evidence to this contention already exists in alcoholic cirrhosis, another disease model of sympathetic overactivation. In this condition, Esler et al 21 have previously demonstrated that sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacological suppression with clonidine than was the systemic sympathetic outflow. Although the cardiac effects of sympathoinhibitory treatments in CHF have been previously studied, [12][13][14] little work has been performed with regards to renal sympathetic tone.…”

Section: Discussionmentioning

confidence: 99%

“…23 Although the effects of carvedilol on cardiac and systemic sympathetic activity have been studied, 24 possible effects on renal sympathetic tone remain to be investigated. In hepatic cirrhosis, Esler et al 21 have demonstrated increased sympathetic neural outflow to the kidneys in humans, with a reduction in renal sympathetic tone and an increase in glomerular filtration rate with intravenous clonidine. However, to our knowledge, the effects of clonidine on renal sympathetic tone in human CHF have not been previously investigated.…”

Section: Discussionmentioning

confidence: 99%

Regional Sympathetic Effects of Low-Dose Clonidine in Heart Failure

et al. 2003

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Abstract-This study examined the effects of low doses of intravenous clonidine on regional and global sympathetic nervous system activity in heart failure. In heart failure, adrenoceptor-blocking treatments have a limited sphere of activity. Centrally acting sympatholytic therapies should be further investigated, with a specific emphasis on targeting cardiac and renal sympathetic overactivity. In 10 patients with moderate-severe congestive heart failure, we examined the effect of intravenous clonidine on systemic, cardiac, and renal sympathetic activity and on brain monoamine turnover using the norepinephrine spillover method. In addition, we assessed the effect of clonidine on cardiac release of the sympathetic cotransmitter neuropeptide Y. A dose of 1 g/kg of clonidine resulted in a fall in cardiac (326Ϯ73 to 160Ϯ40 pmol/min, PϽ0.001), renal (2.5Ϯ0.6 to 1.5Ϯ0.3 nmol/min, Pϭ0.01), and global norepinephrine spillover (4.0Ϯ0.6 to 3.1Ϯ0.5 nmol/min, PϽ0.01), with a significantly disproportionate reduction in cardiac versus total-body sympathetic activity (PϽ0.05). No significant changes in cardiac neuropeptide Y release or in central monoamine turnover were demonstrated. Clonidine, at modest doses, significantly attenuates cardiac and renal sympathetic tone in heart failure. In addition to the beneficial effects of antiadrenergic therapy in the heart, the renal sympatholytic effect may counter the salt and water retention that is a hallmark of the condition.

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Increased Sympathetic Nervous Activity and the Effects of Its Inhibition with Clonidine in Alcoholic Cirrhosis

Cited by 111 publications

References 32 publications

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

Obesity Paradox in Hypertension

Regional Sympathetic Effects of Low-Dose Clonidine in Heart Failure

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