Indirect Analysis of Nitric Oxide and Quantitation of Selective Nitric Oxide Synthase Inhibitors in Microdialysate Samples

While a longstanding body of evidence has suggested that nitric oxide plays a key role in maintaining vascular tone, work over the last decade has indicated that nitric oxide also is an important messenger in the central nervous system. Due to the extremely labile nature of this molecule, quantitation in bulk brain tissue is problematic. Indirect methods of analysis, therefore, have been developed, with the use of microdialysis technology for sample collection. To probe the physiologic and pharmacologic importance of nitric oxide, a variety of nitric oxide synthase inhibitors also have been identified and are amenable to quantitative analysis by standard chromatographic techniques in brain tissue microdialysate. The use of the microdialysis approach for the combined purpose of measuring concentrations of nitric oxide synthase inhibitors at the site of action and changes in nitric oxide content at that site illustrates the power of microdialysis in studies designed to elucidate the linkage between drug concentration (pharmacokinetics) and drug action (pharmacodynamics). This chapter is intended to describe the experimental design, procedural issues, and types of data associated with the use of brain microdialysis to explore the role of nitric oxide in central nervous system pharmacokinetics and pharmacodynamics.