ABSTRACT
NO has a multiplicity of physiologic and pathophysiologic effects which may be either beneficial or detrimental, depending largely on the level of NO synthesis and various additional factors such as the concentration and type of reactive oxygen species at the local site of NO synthesis. Accordingly, factors that regulate cellu lar NO synthesis rates play a major role in determining the physiologic impact of NO production. Maximal cellular capacity for NO synthesis is determined by the intracellular content of NOS. In the case of eNOS and nNOS, expression is largely constitutive and enzyme activity is dynamically regulated by changes in intracel lular calcium flux. In the case of iNOS, it is the expression of the enzyme itself that is regulated, and its activity is independent of changes in intracellular calcium. Nonetheless, it is important to recognize that actual rates of cellular NO produc tion by any of the NOS isoforms are determined by additional factors, such as avail ability of the various substrates and cofactors required by NOS (reviewed in 1).
