Altered renal and platelet arachidonic acid metabolism in cirrhosis.
Urinary excretion rates of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane (TX) B2 were evaluated in three groups of cirrhotic patients [without ascites (group 1, 13 cases), with ascites and normal renal function (group 2, 15 cases), and with ascites and renal failure (group 3, 5 cases)] and in 14 healthy controls. All urinary arachidonate metabolites were significantly increased in group 2 patients. Patients with renal failure showed lower PGE2, PGF2 alpha, and TXB2 values than those from group 2; PGF2 alpha values were also lower than controls. Platelet TXA2 production during whole blood clotting was significantly reduced in all groups of patients. Administration of low-dose aspirin and sulindac, two cyclooxygenase inhibitors selectively sparing renal cyclooxygenase activity, effectively inhibited platelet TXA2 production without affecting urinary TXB2 excretion, thus ruling out platelets as a possible source of urinary TXB2. We conclude that patients with ascites and normal renal function show an overall activation of the renal PG system. Renal production of vasodilating PGE2 and PGI2 may be involved in supporting renal function in these patients. A reduced platelet synthesis of proaggregatory TXA2 also occurs in cirrhotic patients. This may play a role in the bleeding tendency of cirrhosis.
Laffi
G
G
La Villa
G
G
Pinzani
M
M
Ciabattoni
G
G
Patrignani
P
P
Mannelli
M
M
Cominelli
F
F
Gentilini
P
P
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D058186:Acute Kidney Injury / Q000652:urine; D000328:Adult; D000368:Aged; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D003404:Creatinine; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost; D015232:Dinoprostone; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D011458:Prostaglandins E / Q000652:urine; D011460:Prostaglandins F / Q000652:urine; D012084:Renin-Angiotensin System; D013467:Sulindac / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000652:urine
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D011460:Prostaglandins F; D013467:Sulindac; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone; D001241:Aspirin