Renin-angiotensin-aldosterone system in cirrhosis.

Wilkinson, Stephen; Williams, Roger

doi:10.1136/gut.21.6.545

Cited by 60 publications

(19 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the presence of BK Ca ␤-subunit is not necessary for the effect of CO, whereas on the contrary, it is essential for the stimulating effect of NO (Wu et al, 2002). The decreased expression of ␤1-subunit may be due to activation of the Renin-Angiotensin-Aldosterone system present in ascitic cirrhosis (Wilkinson and Williams, 1980;Schrier et al, 1988) because ␤1-subunit synthesis is inhibited by high levels of angiotensin II (Amberg et al, 2003b). However, the decreased presence of ␤1-subunit seems not sufficient to inhibit the action of BK Ca because of the increased expression of the ␣-subunits and of the increased expression of HO, which through CO stimulates BK Ca independently from ␤1-subunits.…”

Section: Mesenteric Vasodilatation In Cirrhosis 193mentioning

confidence: 99%

Carbon Monoxide-Mediated Activation of Large-Conductance Calcium-Activated Potassium Channels Contributes to Mesenteric Vasodilatation in Cirrhotic Rats

Bolognesi

Sacerdoti²,

Piva³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Large-conductance calcium-activated potassium channels (BK Ca s) are important regulators of arterial tone and represent a mediator of the endogenous vasodilator carbon monoxide (CO). Because an up-regulation of the heme oxygenase (HO)/CO system has been associated with mesenteric vasodilatation of cirrhosis, we analyzed the interactions of BK Ca and of HO/CO in the endothelium-dependent dilatation of mesenteric arteries in ascitic cirrhotic rats. In pressurized mesenteric arteries (diameter, 170 -350 m) of ascitic cirrhotic rats, we evaluated the effect of inhibition of BK Ca , HO, and guanylylcyclase on dilatation induced by acetylcholine and by exogenous CO; and HO-1 and BK Ca subunit protein expression. Inhibition of HO and of BK Ca reduced acetylcholine-induced vasodilatation more in cirrhotic rats than in control rats, whereas inhibition of guanylyl-cyclase had a similar effect in the two groups. CO was more effective in cirrhotic rats than in control rats, and the effect was hindered by BK Ca inhibition. The expression of HO-1 and of BK Ca ␣-subunit was higher in mesenteric arteries of cirrhotic rats compared with that of control animals, whereas the expression of the BK Ca ␤1-subunit was lower. In conclusion, an overexpression of BK Ca ␣-subunits, possibly due to HO up-regulation with increased CO production, participates in the endothelium-dependent alterations and mesenteric arterial vasodilatation of ascitic cirrhotic rats.Mesenteric arterial vasodilation is a key mechanism in the pathophysiology of the hyperdynamic circulatory syndrome of cirrhosis. This syndrome is responsible for serious complications, such as ascites, hepatorenal syndrome, and gastrointestinal hemorrhage. The pathophysiological mechanism that supports the vasodilation of mesenteric arteries in cirrhosis is a decrease in the response of the arteries to vasoconstricting agents (Sieber et al., 1993), caused by an increase in vasodilating substances of endothelial origin, such as nitric oxide (NO), prostacyclin, and, as recently demonstrated, carbon monoxide (CO) (Wiest and Groszmann, 1999;Fernandez et al., 2001;Gonzales-Abraldes et al., 2002).We have recently shown that an increased action of the heme oxygenase (HO)/CO system plays a role in the hyporesponsiveness of small resistance mesenteric arteries to phenylephrine (PE) only in the advanced stage of experimental cirrhosis (Bolognesi et al., 2005). Therefore, the increased activity of the HO/CO system may participate in the evolution of cirrhosis from compensated to decompensated.HO is a microsomal enzyme with two main distinct isoforms: the inducible isoenzyme HO-1 and the constitutive one HO-2 (Zhang et al., 2001;Johnson et al., 2003a). It is the rate-limiting enzyme in the degradation of heme to biliverdin, CO, and free iron (Motterlini et al., 1998). CO, generated by HO in endothelial and smooth muscle layers of arterial vessels, modulates vascular tone by inducing relaxation of vascular smooth muscle cells through stimulation on soluble guanylyl cyclase (sGC) and ope...

show abstract

Section: Mesenteric Vasodilatation In Cirrhosis 193mentioning

confidence: 99%

Carbon Monoxide-Mediated Activation of Large-Conductance Calcium-Activated Potassium Channels Contributes to Mesenteric Vasodilatation in Cirrhotic Rats

Bolognesi

Sacerdoti²,

Piva³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Moreover, only one third of the patients with ascites and without renal failure have an activated renin-angiotensin-aldosterone system [3]. These data were interpreted by some in favor of the existence of an increased effective intravascular volume in many cirrhotic patients ('over flow theory') [3]. We have recently suggested that the high uric acid clearances frequently observed in cirrhosis [5][6][7] are secondary to an increased effective vascular volume (EVV) [6,7], The relationship between 'volemia' and uric acid clearance in cirrhosis is further suggested in this paper by the finding of a strong negative correlation between frac-1 This work was supported by a grant from the Ministère de la Politique Scientifique (Actions Concernées).…”

Section: Introductionmentioning

confidence: 99%

“…Aldosterone is considered an important hormone in the sodium retention of cirrhotic patients [1], In cirrhotics without fluid retention, plasma aldosterone concentra tion and urine aldosterone excretion, expressed as a function of urine sodium excretion, are reduced [2][3][4]. Moreover, only one third of the patients with ascites and without renal failure have an activated renin-angiotensin-aldosterone system [3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between Aldosterone and Sodium, Potassium, and Uric Acid Clearance in Cirrhosis with and without Ascites

Decaux¹,

Hanson²,

Cauchie³

et al. 1986

Nephron

View full text Add to dashboard Cite

We have suggested that cirrhotic patients with high uric acid clearances had an increased effective vascular volume. This hypothesis was tested by studying the relationship between the excretion of uric acid, sodium, potassium, and aldosterone in cirrhosis. In 29 consecutive cirrhotic patients, of whom 17 had ascites, and in a control group, the logarithm of urinary sodium and aldosterone excretion highly correlated in control (r = – 0.79, p < 0.001) and cirrhotic patients without (r= – 0.72, p < O.Ol) and with (r= – 0.80, p < 0.001) ascites. The regression line significantly shifted to the left in the cirrhotic patients (p < 0.001). The urinary ratio K/K + Na also correlated with urinary aldosterone in controls (r= +0.66, p < 0.001) and in cirrhotic patients (r= +0.77, p < 0.001); this regression line shifted to the right in cirrhosis patients (p < 0.02). The fractional uric acid excretion significantly correlated with urinary aldosterone only in cirrhotic patients (r = – 0.76, p < 0.001). These data confirmed the existence of hypoaldosteronism in many cirrhotic patients and are consistent with tubular hypersensitivity to aldosterone and emphasize the major role of the effective vascular volume in the control of urid acid clearance in cirrhosis.

show abstract

“…Although several neurohumoral alterations have been described in patients with well-established hepatic cirrhosis [3][4][5][6], it is possible that the physiopathological changes observed are not the same as those occurring in earlier stages of the disease. In fact, some results from cirrhotic patients [7] or from nonascitic cirrhotic rats [8] are not absolutely comparable to those previously de scribed.…”

Section: Introductionmentioning

confidence: 99%

Urinary Excretion and Glomerular Synthesis of Prostaglandin E<sub>2</sub> and Prostaglandin F<sub>2α</sub> in Cirrhotic, Non-Ascitic Rats: The Effects of Sodium Overload

Santos¹,

Rodríguez‐Puyol²,

Blanchart³

et al. 1988

Nephron

View full text Add to dashboard Cite

The urinary excretion of aldosterone, kallikrein and prostaglandin E₂ (PGE₂) was studied in sodium-retaining (RC) and nonretaining (NRC), nonascitic cirrhotic rats, under basal conditions and after an oral sodium load (5 mmol). The glomerular synthesis of PGE₂ was measured in RC rats under the same conditions. Both groups of cirrhotic animals showed a decreased urinary excretion of PGE₂. Isolated glomeruli of RC rats produced less PGE₂than those of the control animals, both under basal conditions and after the sodium load. The NRC group was the only one able to increase the urinary excretion of kallikrein in response to the sodium load. These findings could contribute to explain the early physiopathological events of hepatic cirrhosis.

show abstract

Renin-angiotensin-aldosterone system in cirrhosis.

Cited by 60 publications

References 52 publications

Carbon Monoxide-Mediated Activation of Large-Conductance Calcium-Activated Potassium Channels Contributes to Mesenteric Vasodilatation in Cirrhotic Rats

Carbon Monoxide-Mediated Activation of Large-Conductance Calcium-Activated Potassium Channels Contributes to Mesenteric Vasodilatation in Cirrhotic Rats

Relationship between Aldosterone and Sodium, Potassium, and Uric Acid Clearance in Cirrhosis with and without Ascites

Urinary Excretion and Glomerular Synthesis of Prostaglandin E<sub>2</sub> and Prostaglandin F<sub>2α</sub> in Cirrhotic, Non-Ascitic Rats: The Effects of Sodium Overload

Contact Info

Product

Resources

About