Neuronal nitric oxide synthase and human vascular regulation.
Bottom Line: The conventional notion that endothelial NO synthase (eNOS)-derived NO is largely responsible for both effects has been challenged by first-in-human studies with a selective inhibitor of neuronal NOS (nNOS), S-methyl-l-thiocitrulline (SMTC).These results are consistent with a significant body of experimental studies suggesting that nNOS plays an important role in the local regulation of vessel tone in other species, independent of the effects of nNOS-derived NO in the central nervous system.These emerging data suggest that eNOS and nNOS have distinct roles in the physiologic local regulation of human microvascular tone in vivo and pave the way for further detailed investigation of the relative contribution of nNOS and eNOS in vascular regulation in human disease.
Affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, United Kingdom.Show MeSH
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Mentions: The conventionally accepted notion that tonic NO generation by endothelial eNOS regulates basal microvascular tone and blood flow is challenged by emerging data indicating that basal microvascular tone may be primarily regulated by local nNOS-derived NO (at least in the human forearm and coronary circulations), whereas eNOS may be responsible for changes in tone occurring in response to agonists or shear stress (Figure 3). The potentially independent regulation of basal flow versus stimulated endothelium-mediated increases in blood flow may account for the poor correlation between these two aspects of vascular function in clinical studies, especially in disease settings such as those that predispose to atherosclerosis where eNOS dysfunction may be more prominent.
Affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, United Kingdom.