Nitric oxide regulates the activity of matrix metalloproteinases in the feto-placental unit of diabetic rats.

PUSTOVRH C, JAWERBAUM A, CAPOBIANCO E, WHITE V, MARTÍNEZ N, HIGA R, LÓPEZ-COSTA JJ, GONZÁLEZ E.

Santiago de Chile, Chile

Simposio; 2nd Latin-American symposium on maternal-fetal interaction and placenta: Research & Clinical studies; 2005

Sociedad Latino-Americana de Interacción Materno Fetal y Placenta

Matrix metalloproteinases (MMPs) are enzymes associated with tissue remodeling and growth. Overexpression of MMPs have previously been detected in the feto-placental unit of diabetic rats, an alteration probably involved in non-controlled matrix degradation and incorrect cellular migration. Nitric oxide (NO) levels are increased in fetuses and placenta from diabetic rats. In different cell types, NO induces MMPs activation. The present work evaluated the influence of NO on MMP2 and MMP9 activities in the feto-placental unit of diabetic rats at midgestation. Methods: Rats were made diabetics by administration of streptozotocin (90mg/Kg) to neonates, a method that leads to mild hyperglycemia (150-230 mg/dl) in the adult. Fetal and placental tissues (maternal and fetal placental sides) from diabetic rats (D) and controls (C) were evaluated on day 13.5 of pregnancy. NO synthase (NOS) activity was evaluated in situ by NADPH-diaphorase (NADPH-d) histochemistry. The effect of NO on MMP2 and MMP9 activities were measured after 1 h incubation without additions or in the presence of either a NO donor (sodium nitroprusside (NP) 600 mM) or a NOS inhibitor (L-NAME 600 mM). Results: NADPH-d activity was enhanced in D placenta when compared to C, mostly in the labyrinth zone. In C and D placenta, NP additions increased MMP9 activity (30%, p<0.05) in the maternal side while NAME additions reduced MMP9 and MMP2 activities in both maternal (22%, p<0.05) and fetal (20%, p<0.05) sides. In C and D fetuses, NP additions increased MMP2 activity (30% and 48% respectively, p<0.01) while NAME reduced its activity (25% and 40% respectively, p<0.01). Conclusions: Our results showed that NO positively regulates MMPs activation. In maternal diabetes, overactivation of MMPs in the feto-placental unit may be the result of increased NO levels and may lead to abnormal remodeling processes.