ABSTRACT
Simultaneous determination of urinary excretion rates of primary unmetabolized prostanoids and their enzymatic metabolites were performed by gas chromatography-mass spectrometry (GC/MS) or tandem mass spectrometry (GC/MS/MS). Changes in kidney function were induced by acute (4 h) volume expansion. Despite marked changes in urine flow, GFR, urinary pH, osmolality, sodium and potassium excretion, only a insignificant or transient rise in the enzymatic prostanoid metabolites (2,3-dinor-6-keto-PGF1 alpha, PGE-M, 2,3-dinor-TxB2 and 11-dehydro-TxB2) was observed. The excretion rates of the primary prostanoids were elevated in parallel with the rise in urine flow: PGE2 rose (p less than 0.05) from 14.2 +/- 4.0 to 86.2 +/- 20.7, PGF2 alpha from 60.0 +/- 4.9 to 119.8 +/- 24.0, 6-keto-PGF2 alpha from 7.2 +/- 1.3 to 51.5 +/- 17.0, and TxB2 from 11.2 +/- 3.3 to 13.6 +/- 3.6 ng/h/1.73 m2 (means +/- SEM) at the maximal urine flow. Except for 6-keto-PGF1 alpha and TxB2, this rise in urinary prostanoid levels was only transient despite a sustained fourfold elevated urine flow. We conclude that urine flow rate acutely affect urine prostanoid excretion rates, however, over a prolonged period of time these effects are not maintained. The present data support the concept that urinary levels of primary prostanoids mainly reflect renal concentrations whereas those of enzymatic metabolites reflect systemic prostanoid activity. From the excretion pattern of TxB2 one can assume that this prostanoid represents renal as well as systemic TxA2 activity.
Subject(s)
Blood Volume , Prostaglandins/urine , Thromboxane B2/urine , 6-Ketoprostaglandin F1 alpha/analogs & derivatives , 6-Ketoprostaglandin F1 alpha/urine , Adult , Dinoprost , Dinoprostone , Diuresis , Female , Gas Chromatography-Mass Spectrometry , Glomerular Filtration Rate , Humans , Hydrogen-Ion Concentration , Kidney/physiology , Male , Osmolar Concentration , Prostaglandins E/urine , Prostaglandins F/urine , Thromboxane B2/analogs & derivatives , UrineABSTRACT
During prospective studies of indomethacin treatment of symptomatic patent ductus arteriosus, the question arose whether aminoglycosides alter renal prostaglandin metabolism. Adopting the matched-pair method, we retrospectively analyzed creatinine clearances, urine output and renal PGE2 and PGF2 alpha excretion in preterm infants with and without aminoglycosides. No consistent differences of any of these parameters within the matched pairs could be demonstrated. Indomethacin induced comparable reductions of creatinine clearances in patients with and without aminoglycoside pretreatment. Discrepancies with animal studies and clinical implications of these results are discussed.
