Teratological consequences of nitric oxide synthesis inhibition.
Nitric oxide (NO) is generated by a family of NO synthase (NOS) enzymes, including endothelial (eNOS), inducible (iNOS) and neuronal (nNOS). NO is an important bioregulator of a wide variety of physiological processes. Recent experimental evidence indicates that inhibition of NO synthesis can lead to teratogenesis. The current review focuses on this aspect of NOS. Exposure of pregnant rodents to non-selective NOS inhibitors, such as N(G)-nitro-L-arginine-methyl ester (L-NAME) and N(G)-nitro-L-arginine (L-NNA), has been linked to limb reduction defects. The teratogenic phenotype, characterized by hemorrhage and transverse terminal tissue destruction, has been regarded to be compatible with a vascular origin. The critical time for teratogenic response was traced to advanced stages of gestation. Similar limb reduction defects have been described in mice deficient in eNOS, but not in other NOS isoforms. Several observations have led to the proposal that hypoxia and possible consequential generation of reactive oxygen species are involved in the causation of NOS inhibitors induced limb defects.
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università G. d'Annunzio, Via dei Vestini, 66013 Chieti, Italy. tiboni@unich.it
Gian Mario
GM
Tiboni
Ettore
E
Clementini
D000014:Abnormalities, Drug-Induced / Q000503:physiopathology*; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005865:Gestational Age; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control; D006801:Humans; D017880:Limb Deformities, Congenital / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control; D009569:Nitric Oxide / Q000009:adverse effects* / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase