Increased Synthesis of Systemic Prostacyclin in Cirrhotic Patients

Guarner, Francisco; Guarner, Carlos; Prìeto, Jesús; Colina, Inmaculada; Quiroga, Jorge; Casas, Josefina; Freixa, Roger; Roselló, J.; Gelpí, E.; Balanzó, J.

doi:10.1016/0016-5085(86)91124-8

Cited by 60 publications

(30 citation statements)

References 44 publications

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“…PLA 2 activity migrated as a single peak, eluting at approximately 0.35 mol/L NaCl, the elution position of cPLA 2 (Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

“…Potential roles of groups I and II sPLA 2 include platelet aggregation, inflammation in rheumatic diseases, and proliferative effects in cancer cells. 13,22 Group IV PLA 2 (also known as cPLA 2 ) is an intracellular form that is selective for arachidonic acid and is regulated by changes in intracellular calcium and protein phosphorylation. 8,18,23,24 In most cell types it is therefore the dominant enzyme in controlling eicosanoid production.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] In these studies, cirrhotic patients with ascites without renal failure showed an increased urinary excretion of PGs, mainly prostaglandin E 2 , 6-ketoprostaglandin F 1a (a stable metabolite of prostaglandin I 2 ), and thromboxane B 2 (a stable metabolite of thromboxane A 2 ), compared with control subjects and cirrhotic patients without ascites. Similarly, rats with experimental cirrhosis and ascites also exhibited increased urinary PG excretion.…”

mentioning

confidence: 98%

“…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. 8 Multiple isoforms of PLA 2 have been described that differ in their substrate specificity, Ca 2ϩ dependency, and subcellular localization. 12,13 The present study was undertaken to measure the activity of PLA 2 in kidney and aortic tissue from cirrhotic rats with carbon tetrachloride-induced cirrhosis and ascites.…”

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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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“…PLA 2 activity migrated as a single peak, eluting at approximately 0.35 mol/L NaCl, the elution position of cPLA 2 (Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

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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“…[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.…”

mentioning

confidence: 99%

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

et al. 2005

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Hepatorenal Syndrome

et al. 1993

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Hepatorenal syndrome is a life-threatening complication of severe liver disease. It is generally accepted that the syndrome is the final stage of complex hemodynamic derangements associated with portal hypertension, ie, peripheral arterial vasodilation, effective hypovolemia, and hyperkinetic status. In spite of reduced systemic resistances, intrarenal vascular resistances are increased. This is probably the consequence of the activation of systemic vasoactive factors, such as the renin-angiotensin system, the sympathetic nervous system, and vasopressin aimed at restoring arterial filling pressure. Recently, it has been shown that intrarenal vasoconstrictors, such as leukotrienes and endothelins, are activated with the progression of liver disease. The renal vasoconstriction is counterbalanced by the intrarenal hyperproduction of vasodilating prostaglandins and kallikreins. When this balance is lost, for whatever mechanism, the renal vascular resistances dramatically increase and the hepatorenal syndrome develops. In spite of increased knowledge about pathogenesis, the treatment of hepatorenal syndrome remains unresolved. Low-dose dopamine or ornipressin are currently employed in many liver units to avoid further deterioration of renal function in patients with severe liver disease who are waiting for liver transplantation that remains, at present, the only effective treatment for hepatorenal syndrome.

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Increased Synthesis of Systemic Prostacyclin in Cirrhotic Patients

Cited by 60 publications

References 44 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

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

Hepatorenal Syndrome

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