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Excretion of metabolites of prostacyclin and thromboxane by rats with nephrotoxic nephritis: effects of interleukin‐1
Author(s) -
Ward Paul S.,
Fuller Richard W.,
Ritter James M.,
Cashman Stephen J.,
Rees Andrew J.,
Dollery Colin T.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb09844.x
Subject(s) - endocrinology , medicine , excretion , thromboxane , thromboxane a2 , eicosanoid , creatinine , chemistry , renal function , thromboxane b2 , prostacyclin , prostaglandin , platelet , biochemistry , arachidonic acid , enzyme
1 To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti‐glomerular‐basement‐membrane antibodies (a‐GBM), products derived from thromboxane A 2 (TXA 2 ) and prostacyclin (PGI 2 ) were measured in 24 h urine collections before and after a‐GBM. 2 Administration of a‐GBM (9.5 mg) caused albuminuria, decreased creatinine clearance, increased numbers of intra‐glomerular neutrophils and increased excretion of TXB 2 , 2,3‐dinor‐TXB 2 (products of TXA 2 ) and 6‐oxo‐PGF 1α and 2,3‐dinor‐6‐oxo‐PGF 1α (products of PGI 2 ) at 24 h. 3 Interleukin‐1 (IL‐1 β ; 5 μg) alone caused an increase in PGI 2 metabolite excretion but had no effect on TXA 2 metabolites. It had no effect on creatinine clearance but increased numbers of glomerular neutrophils by approximately 4–5 fold compared to a‐GBM. 4 Pretreatment of rats with IL‐1 β before a‐GBM synergistically increased albumin excretion but only additively increased eicosanoid excretion. Numbers of intra‐glomerular neutrophils and creatinine clearance were unchanged compared to IL‐1 β alone. 5 The cyclo‐oxygenase inhibitor, ibuprofen (10 mg kg −1 i.p., twice daily for 4 days) inhibited both serum TXB 2 production and urinary prostaglandin excretion. It also caused an almost complete attenuation of albumin excretion. Creatinine clearance and glomerular neutrophils remained unchanged after a‐GBM/IL‐1 β.6 We conclude that the 50% inhibition of thromboxane production induced by ibuprofen does not modify the fall in creatinine clearance of accumulation of neutrophils in the glomerulus caused by the a‐GBM. This degree of inhibition of eicosanoid production was associated with a striking decrease in proteinuria, but this may reflect a haemodynamic rather than a disease modifying action.