Effects of a thromboxane synthetase inhibitor on established immune complex glomerulonephritis in dogs.
Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indolectanoic acid (CGS 12970)/kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/microns 3 were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Grauer
G F
GF
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
Frisbie
D D
DD
Longhofer
S L
SL
Cooley
A J
AJ
D000818:Animals; D000906:Antibodies / Q000097:blood; D003208:Concanavalin A / Q000276:immunology; D003404:Creatinine / Q000652:urine; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000662:veterinary; D005921:Glomerulonephritis / Q000188:drug therapy / Q000662:veterinary*; D007105:Immune Complex Diseases / Q000188:drug therapy / Q000662:veterinary*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011507:Proteinuria / Q000662:veterinary; D011725:Pyridines / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000906:Antibodies; D011725:Pyridines; D003208:Concanavalin A; D013929:Thromboxane B2; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D003404:Creatinine; D013930:Thromboxane-A Synthase