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Increased total body synthesis of prostacyclin in rats with adjuvant arthritis
D O Stichtenoth1, N Selve, D Tsikas
1Department of Clinical Pharmacology, Hannover Medical School, Germany.
Abstract:
In rats with adjuvant arthritis we measured the urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha, 7 alpha-hydroxy-5,11-dioxo-tetranor-prosta-1,16- dioic acid (PGE-M) and 2,3-dinor-thromboxane-B2, reflecting total body synthesis of prostacyclin, thromboxane and the E-prostaglandins, respectively. The urinary prostanoid metabolites were assessed by gas chromatography/tandem mass spectrometry using stable isotope internal standards. We found a more than 10-fold increase of urinary 2,3-dinor-6-oxo-PGF1 alpha excretion and a 5-fold higher urinary excretion of PGE-M in adjuvant arthritic rats as compared to non-arthritic control rats (p < 0.001; n = 12, each). There was no significant difference in urinary 2,3-dinor-thromboxane-B2 excretion between arthritic rats and control animals. Our data show a dramatic increase of urinary 2,3-dinor-6-oxo-PGF1 alpha excretion reflecting increased total body prostacyclin synthesis. It can be assumed that prostacyclin plays a role in generalized inflammatory reactions, comparable to that of the E-prostaglandins.