title: Thromboxane-receptor blockade increases water diuresis in cirrhotic patients with ascites.
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.
authors.affiliation: Istituto di Clinica Medica II, University of Florence School of Medicine, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Laffi
authors.forename: F
authors.initials: F
authors.lastname: Marra
authors.forename: V
authors.initials: V
authors.lastname: Carloni
authors.forename: G
authors.initials: G
authors.lastname: Azzena
authors.forename: M L
authors.initials: ML
authors.lastname: De Feo
authors.forename: M
authors.initials: M
authors.lastname: Pinzani
authors.forename: C
authors.initials: C
authors.lastname: Tosti-Guerra
authors.forename: P
authors.initials: P
authors.lastname: Gentilini
mesh_terms: D000368:Aged; D001201:Ascites / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism*; D004231:Diuresis; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D012964:Sodium / Q000652:urine; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
chemical_list: D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013929:Thromboxane B2; D013928:Thromboxane A2; C049855:ONO 3708; D012964:Sodium