Inhibition of nitric oxide synthesis causes preterm delivery in the mouse.
The aim of the present study was to investigate whether an inhibitor of nitric oxide (NO) synthesis provokes preterm delivery in a mouse model. ICR (CD-1) mice were injected s.c. with N(G)-nitro-L-arginine methyl esther (L-NAME) at 0, 40, 70 or 100 mg/kg on gestation day (GD) 15.5 and 16. Delivery was considered preterm if it occurred before GD 18. In a satellite study, the potential ability of the NO donor sodium nitroprusside (SNP) to prevent L-NAME-induced preterm delivery was tested. Five hours before the initiation of treatment regimen with L-NAME at 70 mg/kg, mice were implanted s.c. with micro-osmotic pumps infusing SNP at 0 or 10 microg/kg/min continuously for 3 days. Administration of L-NAME evoked preterm delivery. This response was noted in 64 and 60% of animals treated with 70 and 100 mg/kg L-NAME respectively (P < 0.05 versus control value). Infusion with SNP provided complete and significant (P < 0. 05 versus positive control value) protection from L-NAME-initiated preterm delivery. This is the first report to reveal that an inhibitor of NO synthesis initiates preterm delivery in a mouse model.
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università 'G. d'Annunzio', Chieti, Italy. tiboni@unich.it
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Giampietro
D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D007752:Obstetric Labor, Premature / Q000139:chemically induced* / Q000378:metabolism*; D011247:Pregnancy
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester