Device for In Vivo Delivery of Nitric Oxide

Nitric oxide (NO) is a free-radical gas that is implicated in many important physiological roles,including such fundamental processes as blood pressure regulation and memory formation. While muchindirect research has been performed on systems that use NO, studies of direct in vivo application ofNO have been hindered by the volatility of NO and the potential toxicity of currently-used methods ofdelivering it. A new method for delivering NO is proposed, based on the availability of new, "caged"compounds. These substances conserve their biological activity until activated with light stimuli of theappropriate wavelength. A sequential, three stage experimental approach will be employed to prove thefeasibility of the method, culminating in the demonstration of feasibility in an experimental animal model.In addition to enabling NO delivery in an animal with intact neuronal and vascular circuits, the methodwill apply to other neurotransmitters. Based on the design flexibility, a wide range of potentialapplications are envisioned: in micropharmacology experiments (where the delivery method promisesbetter temporal resolution and receptor coverage than currently available micropharmacologicaltechniques, including microiontophoresis and pressure ejection); in new in vivo and in vitro macropharma-cological approaches; and in new photodynamic cancer therapies.