Effects of thromboxane synthetase inhibition on immune complex glomerulonephritis.
To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histological changes associated with immune complex glomerulonephritis.
Longhofer
S L
SL
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
Frisbie
D D
DD
Johnson
H C
HC
Culham
C A
CA
Cooley
A J
AJ
Schultz
K T
KT
Grauer
G F
GF
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D003208:Concanavalin A / Q000276:immunology; D015232:Dinoprostone / Q000652:urine; D004195:Disease Models, Animal; D004285:Dogs; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000209:etiology / Q000662:veterinary*; D007105:Immune Complex Diseases / Q000209:etiology / Q000662:veterinary*; D007668:Kidney / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D011725:Pyridines; D003208:Concanavalin A; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D013930:Thromboxane-A Synthase; D015232:Dinoprostone