Abstract
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 NG-nitro- Larginine- methyl ester (L-NAME) and NG-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.
Keywords: nitric oxide, nitric oxide synthase, nitric oxide synthase inhibitors, teratogenesis, limb defects, cardiovascular defects, rat, mouse
Current Pharmaceutical Design
Title: Teratological Consequences of Nitric Oxide Synthesis Inhibition
Volume: 10 Issue: 22
Author(s): Gian Mario Tiboni and Ettore Clementini
Affiliation:
Keywords: nitric oxide, nitric oxide synthase, nitric oxide synthase inhibitors, teratogenesis, limb defects, cardiovascular defects, rat, mouse
Abstract: 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 NG-nitro- Larginine- methyl ester (L-NAME) and NG-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.
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Cite this article as:
Tiboni Mario Gian and Clementini Ettore, Teratological Consequences of Nitric Oxide Synthesis Inhibition, Current Pharmaceutical Design 2004; 10 (22) . https://dx.doi.org/10.2174/1381612043383665
DOI https://dx.doi.org/10.2174/1381612043383665 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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