Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour

• Published in: British journal of pharmacology Vol. 161; no. 4; pp. 844 - 855
• Main Authors: Cella, M, Farina, MG, Dominguez Rubio, AP, Di Girolamo, G, Ribeiro, ML, Franchi, AM
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2010; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Cyclooxygenase 2 Inhibitors - pharmacology; Dinoprost - biosynthesis; Dinoprostone - biosynthesis; Disease Models, Animal; Diseases of mother, fetus and pregnancy; Enzyme Inhibitors - pharmacology; Female; Guanidines - pharmacology; Gynecology. Andrology. Obstetrics; Inflammation - physiopathology; Lipopolysaccharides - toxicity; Medical sciences; Meloxicam; Mice; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Obstetric Labor, Premature - etiology; Obstetric Labor, Premature - physiopathology; Pharmacology. Drug treatments; Pregnancy; Pregnancy. Fetus. Placenta; Premature birth; preterm delivery; prostaglandins; Radioimmunoassay; Research Papers; Thiazines - pharmacology; Thiazoles - pharmacology; uterus; Uterus - metabolism; Pregnancy disorders; Prostaglandin; Arachidonic acid derivatives; Rodentia; Premature delivery; Vertebrata; Mammalia; Prematurity; Mouse; Uterus; Eicosanoid; Animal; Nitric oxide; Female genital system; prostaglandins; Models; preterm delivery
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.00911.x

BACKGROUND AND PURPOSE Maternal infections are one of the main causes of adverse developmental outcomes including embryonic resorption and preterm labour. In this study a mouse model of inflammation‐associated preterm delivery was developed, and used to study the relationship between nitric oxide (NO) and prostaglandins (PGs). EXPERIMENTAL APPROACH The murine model of preterm labour was achieved by assaying different doses of bacterial lipopolysaccharides (LPS). Once established, it was used to analyse uterine levels of prostaglandins E2 and F2α (by radioimmunoassay), cyclooxygenases (COX) and NOS proteins (by Western blot) and NO synthase (NOS) activity. Effects of inhibitors of COX and NOS on LPS‐induced preterm labour were also studied. In vitro assays with a nitric oxide donor (SNAP) were performed to analyse the modulation of prostaglandin production by NO. KEY RESULTS Lipopolysaccharide increased uterine NO and PG synthesis and induced preterm delivery. Co‐administration of meloxicam, a cyclooxygenase‐2 inhibitor, or aminoguanidine, an inducible NOS inhibitor, prevented LPS‐induced preterm delivery and blocked the increase in PGs and NO. Notably, the levels of NO were found to determine its effect on PG synthesis; low concentrations of NO reduced PG synthesis whereas high concentrations augmented them. CONCLUSIONS AND IMPLICATIONS An infection‐associated model of preterm labour showed that preterm delivery can be prevented by decreasing PG or NO production. NO was found to have a dual effect on PG synthesis depending on its concentration. These data contribute to the understanding of the interaction between NO and PGs in pregnancy and parturition, and could help to improve neonatal outcomes.