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: In further studies, Seddon et al. (Seddon et al. 2009) also investigated the potential role of local nNOS in the human coronary circulation. The effects of intracoronary infusion of SMTC were studied in patients undergoing cardiac catheterization who turned out to have angiographically normal coronary arteries. In these subjects, SMTC caused a significant reduction in basal blood flow as assessed by intracoronary Doppler and angiography. However, SMTC had no effect on the increases in flow elicited by intracoronary substance P infusion, which in contrast was inhibited by l-NMMA (Seddon et al. 2009) (Figure 2). These data indicate that the effects of SMTC on basal flow extend to the coronary circulation.
Affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, United Kingdom.