Increased total body synthesis of prostacyclin in rats with adjuvant arthritis.
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.
Stichtenoth
D O
DO
Department of Clinical Pharmacology, Hannover Medical School, Germany.
Selve
N
N
Tsikas
D
D
Gutzki
F M
FM
Frölich
J C
JC
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D003404:Creatinine / Q000652:urine; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D008297:Male; D011453:Prostaglandins / Q000378:metabolism / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine
D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D003404:Creatinine; D011464:Epoprostenol