Systemic and renal production of thromboxane A2 and prostacyclin in decompensated liver disease and hepatorenal syndrome

Moore, Kevin; Ward, Paul S.; Taylor, Graham W.; Williams, Roger

doi:10.1016/0016-5085(91)90284-r

Cited by 65 publications

(38 citation statements)

References 20 publications

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“…The urinary excretion of 2,3-dinor-6-keto-prostaglandin F 1␣ , a prostaglandin I 2 metabolite used to estimate the extrarenal production of prostaglandin I 2 , is increased in patients with cirrhosis, particularly in those with ascites, and correlates inversely with arterial pressure. 2,10 Moreover, the observation that PG synthesis inhibition with indomethacin in patients with cirrhosis or experimental animals with portal hypertension is associated with an increase in systemic vascular resistance and reduction in cardiac output also supports the existence of increased systemic PG synthesis in cirrhosis, which may play a role in the pathogenesis of arterial vasodilation. 38,39 Although our data indicate the existence of an upregulation of cPLA 2 in cirrhosis with ascites, it is also possible that other enzymes of the eicosanoid cascade (i.e., cyclooxygenases) or other isoforms of PLA 2 participate in the increased eicosanoid synthesis characteristic of this condition.…”

Section: Discussionmentioning

confidence: 83%

“…Patients with cirrhosis have high urinary excretion of 2-3-dinor-6-ketoprostaglandin F 1a , a metabolite of prostaglandin I 2 thought to represent an index of systemic prostaglandin I 2 production. 9,10 In spite of this indirect evidence supporting the existence of increased renal and extrarenal production of PGs in cirrhosis, only one recent study has directly assessed the activity of the enzymes involved in PG synthesis. 11 Phospholipase A 2 (PLA 2 ), which hydrolyzes membrane phospholipids at the sn-2 position, has been shown to be the rate-limiting enzyme in eicosanoid production in most cell types.…”

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confidence: 99%

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Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites

et al. 1998

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Indirect evidence suggests that the renal and vascular production of prostaglandins is increased in cirrhosis with ascites. However, the activity of the enzymes regulating the prostaglandin pathway has not been investigated in cirrhosis. The aim of the current study was to determine the activity of phospholipase A 2 (PLA 2 ), the key enzyme in the regulation of prostaglandin synthesis, in kidney and vascular tissue obtained from rats with carbon tetrachlorideinduced cirrhosis and ascites (n ‫؍‬ 9) and control rats (n ‫؍‬ 6). PLA 2 activity was assayed in vitro using [ 14 C]arachidonylphosphatidylcholine (PC) and [ 14 C]arachidonyl-phosphatidylethanolamine (PE) as substrates in the presence of Ca 2؉ . Kidneys from cirrhotic rats had significantly higher PLA 2 activity compared with control rats, with both PC and PE (35 ؎ 5 and 40 ؎ 6 vs. 21 ؎ 2 and 26 ؎ 3 pmol/mg/min, respectively; P F .05 for both). PLA 2 activity was increased in the renal cortex as well as in the renal medulla. Fractionation of the kidney extracts by Mono-Q anionexchange chromatography showed that the elution position of PLA 2 activity corresponded to the cytosolic PLA 2 isoform (cPLA 2 ). Increased amounts of cPLA 2 protein were found in kidney extracts immunoblotted with an anti-cPLA 2 antibody. However, reverse-transcriptase polymerase chain reaction (RT-PCR) analysis did not detect any difference in cPLA 2 mRNA. PLA 2 activity was also higher in aortic tissue from cirrhotic rats than in controls (PC 38 ؎ 5 vs. 26 ؎ 1 and PE 66 ؎ 8 vs. 41 ؎ 3 pmol/mg/min; P F .05 for both). Incubation of renal and aortic extracts from cirrhotic rats with anti-cPLA 2 antibody reduced PLA 2 activity by 64% and 88%, respectively. In conclusion, PLA 2 activity is increased in kidneys and vascular tissue from cirrhotic rats with ascites. This can be accounted for by an induction of cPLA 2 , which would mediate, at least in part, the increased renal and vascular production of prostaglandins in cirrhosis.(HEPA-TOLOGY 1998;27:42-47.)

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Section: Discussionmentioning

confidence: 83%

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confidence: 99%

Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites

et al. 1998

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“…This is thelin). [32][33][34][35][36] To rule out an impaired kidney function caused a further argument against a stimulated NO formation in our by an activation of the renin-angiotensin-system we deterpatients with compensated liver cirrhosis. mined renin and aldosterone in our patients.…”

Section: Discussionmentioning

confidence: 99%

Renal functional reserve and nitric oxide in patients with compensated liver cirrhosis

et al. 1997

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To investigate the role of nitric oxide (NO) with respect to In this context, some authors have postulated that patients with compensated liver cirrhosis already show hyperfiltration kidney function and liver cirrhosis, we evaluated renal function, as well as cyclic guanosine monophosphate (cGMP) and in an unstimulated state, which suggests a preponderate NOformation in the kidney. 9 However, the role of NO with NO x (nitrite/nitrate [NO 3 -/NO 2 -]) as indirect markers of NO formation in plasma and urine at rest and during amino acid respect to renal dysfunction has been ill-defined. Thus, the aim of the present study was two-fold: first, to find out if (aa)-induced glomerular hyperfiltration in patients with Child A liver cirrhosis and portal hypertension (n Å 12), and in renal function is altered in patients with compensated liver cirrhosis (Child A) with respect to glomerular filtration rate healthy controls (n Å 10). Baseline filtration rate (GFR) and effective renal plasma flow (ERPF) were significantly lower (GFR), effective renal plasma flow (ERPF), renal vascular resistance (RVR), and filtration fraction (FF) both before in patients with cirrhosis than in controls (GFR: mean 88 { SD 16 mL/min vs. 106 { 15 mL/min, P Å .01, ERPF: 477 { and during testing renal functional reserve (RFR Å difference between stimulated GFR and baseline GFR) by an amino 93 vs. 561{ 72 mL/min, P Å .002). In both groups amino acid (aa) infusion increased GFR, ERPF, as well as cGMP acid (aa) infusion compared with healthy controls. 5,6,[10][11][12] Second, to evaluate whether changes in renal function correand urinary NO x . Changes in GFR were similar in cirrhotic patients and controls (28.3% { 14% in cirrhotics and 26% { spond to alterations in plasma NO x (nitrite/nitrate [NO 3 -/ NO 2 -]) and cyclic guanosine monophosphate (cGMP) levels 11% in controls), but the degree of aa-induced changes in ERPF was more marked in patients with liver cirrhosis (31.8% as well as renal NO excretion as determined by urinary nitrite/nitrate and cGMP. NO x and cGMP are indirect markers { 17% vs. 18.6% { 12%, P Å .02). Plasma levels of NO x and cGMP were similar in either group at baseline and during aa of NO release, which itself, because of its short half-life, is difficult to determine in humans. infusion, whereas NO x and cGMP excretion in cirrhotics was constantly 14% to 24% lower than in the control group. We tors and vasodilators such as NO. It is also believed that NO served as controls. Throughout the study period all subjects neither is a mediator of renal hyperfiltration following aa infusion. [5][6][7][8] smoked nor took any medication. There were no vegetarians in either group and the participants continued their regular western diet that contained 0.9 { 0.15 g/kg body weight protein, as calculated from the 24-hour urine collection. 13 The 24-hour urinary soAbbreviations: NO, nitric oxide; GFR, glomerular filtration rate; ERPF, effective dium output on the day before the study was 126 { 18 mmol in renal plasma flow; RVR, renal vascu...

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“…[1][2][3][4] One of the rate-limiting steps in the synthesis of prostaglandins is the release of arachidonic acid from membrane phospholipids by the phospholipase A 2 (PLA 2 ) enzyme. It has been reported that a secreted type of PLA 2 , PLA 2 IIA, which plays a crucial role in inflammation, was upregulated in the liver and kidney of rats with cirrhosis.…”

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confidence: 99%

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

et al. 2005

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Systemic and renal production of thromboxane A2 and prostacyclin in decompensated liver disease and hepatorenal syndrome

Cited by 65 publications

References 20 publications

Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites

Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites

Renal functional reserve and nitric oxide in patients with compensated liver cirrhosis

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

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