In Vivo Imaging of Spin-Tapped Nitric Oxide (NO) in Septic-Shock Rats: MRI Spin-Trapping Method

Introduction Nitric oxide (NO) was first appreciated as a biological mediator in its role as endothelial derived relaxing factor, which is responsible for regulation of blood vessel relaxation and its maintenance [ 11. It also became evident that NO was produced in the brain, catalyzed by a nitric oxide synthase (NOS), where NO acts as a synaptic neuronal messenger [2]. NO is a gaseous and highly reactive, short lived free radical. Therefore, direct detection by stabilizing NO with suitable spin-trapping reagents is requisite to estimating the in vivo NO concentration. We have previously employed irondithiocarbamate spin-trapping reagents and have succeeded in direct detection of NO in septic-shock mice by whole body L-band EPR spectroscopy [3]. The in vivo EPR and EPR imaging results reveal that NO is produced mainly in the upper abdomen near the liver [3,4]. While we and other groups have demonstrated the feasibility of EPR imaging in visualizing free radical distribution in vivo, the spatial resolution of most EPR imaging system is not satisfactory enough to resolve much fine structure for specific organs by visualizing the distribution of free radicals, especially where the intrinsic linewidth of the radical is large, such as the spin-trapped NO [4]. In the present study, we employed MRI combined with NO spintrapping reagent to evaluate the feasibility of mapping the distribution of this NO spin-trap complex in septic shock rats.