Nitric oxide formation from glyceryl trinitrate in the developing guinea-pig hippocampus

Glyceryl trinitrate (GTN) is classified as an organic nitrate vasodilator d rug. GTN is considered to be a prodrug because it undergoes biotransformati on at its site of action to form nitric oxide (NO) or a NO adduct, which pr oduces its pharmacologic effect. The objectives of this study were to deter mine whether the hippocampus can biotransform GTN to NO using aerobic condi tions, and whether biotransformation of GTN to NO is age-dependent during p ostnatal life. Time-dependent formation of NO occurred during the incubatio n of 100 muM GTN with 2.5% (w/v) homogenate of guinea-pig hippocampus at 37 degreesC using aerobic conditions. GTN-derived NO formation was similar in magnitude for the three selected postnatal ages that were studied that is, postnatal days 10, 20 and > 60. The data demonstrate that the capacity of the hippocampus for NO formation from GTN is fully developed in the guinea- pig in early postnatal life. In view of these findings, it is conceivable t hat a NO donor drug, selectively metabolized to NO in the hippocampus, coul d be a useful therapeutic intervention to mitigate structural and/or functi onal defects in this brain region resulting from decreased NO formation or availability.