Effect of inducible nitric oxide synthase inhibition by aminoguanidine on insulin-like growth factor binding protein-3 in adjuvant-induced arthritic rats.
This study was designed to investigate whether nitric oxide (NO) mediates changes in insulin-like growth factor binding protein-3 (IGFBP-3) levels in rats with adjuvant-induced arthritis. Male Wistar rats were injected with complete Freund's adjuvant, and 20 days afterwards arthritic and control rats were injected daily with an inhibitor of inducible NO synthase (iNOS), aminoguanidine, or vehicle for 8 days. The increase in serum levels of IGFBP-3 induced by arthritis was exacerbated by aminoguanidine treatment. Arthritis increased IGFBP-3 mRNA levels in the kidney but not in the liver. The inhibition of iNOS did not modify IGFBP-3 gene expression in the kidney or in the liver in arthritic rats. However, the inhibitory effect of arthritis on the proteolysis of IGFBP-3 in serum was potentiated by aminoguanidine administration. These results indicate that arthritis increases serum IGFBP-3 by increasing its synthesis in the kidney and decreasing its proteolysis in serum and that these effects are not mediated by NO.
Ibáñez de Cáceres
Inmaculada
I
Department of Physiology, Faculty of Medicine, Complutense University, Avda. Complutense s/n. 28040 Madrid, Spain.
Priego
Teresa
T
Martín
Ana Isabel
AI
Granado
Miriam
M
López-Calderón
Asunción
A
Villanúa
Maria Angeles
MA
D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006146:Guanidines; D018972:Insulin-Like Growth Factor Binding Protein 3; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine