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Title: Regulation of urinary thromboxane B2 in man: influence of urinary flow rate and tubular transport

Thromboxane B2 (TxB) is excreted in human urine, but the mechanism of renal excretion and the quantitative relationship of urinary TxB to the active parent compound, thromboxane A2, of renal or extrarenal origin is not established. To determine the effects of vasoactive hormones, uricosuric agents and urinary flow rate on TxB excretion, urinary TxB was measured by radioimmunoassay and mass spectrometry, and renal metabolism of blood TxB was determined by radiochromatography of urine after i.v. (3H)-TxB infusions. Basal TxB was 6.7 +/- 1.1 ng/h during an oral water load, and TxB fell with s.g. antidiuretic hormone (to 3.4 +/- 0.4 ng/h, P less than 0.01) and with fluid restriction (to 2.6 +/- 0.5 ng/hr, P . 0.001) in parallel with urinary volume. Urinary excretion of unmetabolized (3H)-TxB also fell (by 56%) with fluid restriction, implicating altered metabolism rather than synthesis as the mechanism of the urinary flow effect. Angiotensin II infusions slightly reduced both TxB and urine volume, consistent with a flow effect. In contrast, probenecid did not alter urine volume, but increased urinary uric acid (by 244%), TxB (from 5.6 +/- 0.9 to 11.1 +/- 2.9 ng/h) and urinary excretion of blood (3H)-TxB (by 243%) by similar amounts (allmore » P less than 0.05), suggesting that TxB is actively reabsorbed in the proximal tubule, similarly to uric acid. Thus, urinary excretion of TxB of renal and extrarenal origin is regulated by proximal and distal tubule factors.« less
Authors:
;
Publication Date:
OSTI Identifier:
6746960
Resource Type:
Journal Article
Resource Relation:
Journal Name: Prostaglandins; (United States); Journal Volume: 27:2
Research Org:
Department of Medicine, University of Southern California, Los Angeles County Medical Center
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ARACHIDONIC ACID; METABOLITES; EXCRETION; RADIOCHROMATOGRAPHY; RADIOIMMUNOASSAY; ANGIOTENSIN; MASS SPECTROSCOPY; METABOLISM; PROSTAGLANDINS; RENAL CLEARANCE; TRITIUM COMPOUNDS; URINE; BIOLOGICAL MATERIALS; BIOLOGICAL WASTES; BODY FLUIDS; CARBOXYLIC ACIDS; CARDIOVASCULAR AGENTS; CHROMATOGRAPHY; CLEARANCE; DRUGS; GLOBULINS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MATERIALS; MONOCARBOXYLIC ACIDS; ORGANIC ACIDS; ORGANIC COMPOUNDS; PROTEINS; RADIOASSAY; SEPARATION PROCESSES; SPECTROSCOPY; TRACER TECHNIQUES; VASOCONSTRICTORS; WASTES 550601* -- Medicine-- Unsealed Radionuclides in Diagnostics