In vivo imaging of spin-trapped nitric oxide in rats with septic shock: MRI spin trapping

Abstract

This paper reports the first in vivo NMR image of the distribution of NO using the 'MRI spin-trapping' technique. NO was complexed with the Fe(II)- chelate spin trap, N-methyl-D-glucamine dithiocarbamate (MGD), verified as (MGD)2-Fe(II)-NO by EPR, and the radical distribution was 'visualized' by MR images. In rats, the (MGD)2-Fe(II)-NO complex was concentrated in the liver displaying significantly enhanced contrast in the vascular structure such as hepatic vein and inferior vena cava. Nitric oxide synthase was verified as the source of NO in rats with septic shock by pre-administration of the competitive inhibitor N-monomethyl-L-arginine, resulting in reduced enhancement. The NO complex was more stable in vivo and a more effective MRI contrast agent than other stable nitrogen containing radicals, such as nitroxides. The MRI spin-trapping method should be a powerful tool for visualizing spatial distributions of free radicals in pathologic organs and tissues when combined with the appropriate radical complexing agent, such as (MGD)2-Fe(II) used in these studies.