Intrarenal thromboxane A2 generation reduces the furosemide-induced sodium and water diuresis in cirrhosis with ascites.
To assess the effects of intrarenal thromboxane A2 generation on furosemide-induced sodium and water excretion we administered furosemide (40 mg i.v.) to 8 nonazotemic cirrhotic patients with ascites and 8 healthy subjects before and after the administration of OKY 046 (200 mg twice orally), a powerful thromboxane-synthase inhibitor. Selective thromboxane-synthase inhibition significantly reduced basal and postfurosemide (1 h) urinary thromboxane B2 excretion in healthy subjects (65% before and 62% after furosemide) as well as in cirrhotic patients (52% before and 67% after furosemide) without affecting urinary prostaglandin E2 and 6-keto prostaglandin F1 alpha excretion. During the first hour after furosemide administration, OKY 046 administration significantly enhanced postfurosemide water excretion (milliliters per minute) in both healthy subjects (from 8.5 +/- 2.0 to 11.6 +/- 2.1, p less than 0.001) and cirrhotic patients (from 1.1 +/- 0.8 to 4.2 +/- 0.5, p less than 0.005), whereas furesemide-induced natriuresis (microequivalents per minute) was significantly increased only in the latter group (from 973 +/- 125 to 1405 +/- 121, p less than 0.05). Our data indicate that intrarenal thromboxane A2 generation, elicited by furosemide administration, may reduce the effects of the drug on water and sodium diuresis. Such a reduction seems to be more marked in the presence of an activated intrarenal prostaglandin system, suggesting that renal thromboxane A2 may represent an additional factor in conditioning the impaired responsiveness to furosemide, which is frequently observed in cirrhotic patients with ascites.
Pinzani
M
M
Istituto di Clinica Medica II, University of Florence, School of Medicine, Italy.
Laffi
G
G
Meacci
E
E
La Villa
G
G
Cominelli
F
F
Gentilini
P
P
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D000368:Aged; D015232:Dinoprostone; D004231:Diuresis; D005260:Female; D005665:Furosemide / Q000652:urine; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D008875:Middle Aged; D011458:Prostaglandins E / Q000652:urine; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology*; D013929:Thromboxane B2 / Q000652:urine
D008689:Methacrylates; D011458:Prostaglandins E; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D005665:Furosemide; D015232:Dinoprostone; C034364:ozagrel