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Thromboxane-receptor blockade increases water diuresis in cirrhotic patients with ascites.
- Source :
-
Gastroenterology [Gastroenterology] 1992 Sep; Vol. 103 (3), pp. 1017-21. - Publication Year :
- 1992
-
Abstract
- This study was undertaken to investigate the role of increased renal thromboxane (TX) A2 production in modulating renal hemodynamics and sodium and water retention in cirrhotic patients with ascites. In a randomized, double-blind, placebo-controlled, crossover trial, 15 nonazotemic cirrhotic patients with ascites and elevated urinary TXB2 excretion received the thromboxane-receptor antagonist ONO-3708 (3 micrograms.kg-1.min-1) in a 4-hour continuous infusion. Administration of ONO-3708 significantly blocked TXA2 receptors; bleeding time showed a twofold increase (432 +/- 65 vs. 131 +/- 17 seconds; P less than 0.005), and platelet aggregation to U-46619 (an agonist of TXA2 receptors) was abolished in all patients studied. The drug induced a significant increase in free water clearance (3.06 +/- 0.70 vs. 1.72 +/- 0.57 mL/min; P less than 0.001) and diuresis (4.74 +/- 0.79 vs. 3.94 +/- 0.66 mL/min; P less than 0.05) compared with placebo, as well as a significant (14%) increase in renal plasma flow. The increases in both free water clearance and diuresis induced by ONO-3708 were directly related to basal urinary TXB2 excretion. These results suggest a role for renal TXA2 as a modulator of water handling in cirrhotic patients with ascites.
- Subjects :
- Aged
Double-Blind Method
Female
Glomerular Filtration Rate drug effects
Humans
Male
Middle Aged
Receptors, Thromboxane
Sodium urine
Thromboxane A2 antagonists & inhibitors
Thromboxane A2 pharmacology
Thromboxane B2 urine
Urodynamics drug effects
Ascites metabolism
Body Water metabolism
Diuresis
Liver Cirrhosis metabolism
Receptors, Prostaglandin antagonists & inhibitors
Thromboxane A2 analogs & derivatives
Thromboxane A2 biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 103
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 1386823
- Full Text :
- https://doi.org/10.1016/0016-5085(92)90037-y