Experimental evidence suggesting that nitric oxide diffuses from tissue into blood but not from blood into tissue

The aim of this study was to evaluate in vivo whether nitric oxide (NO) is able to diffuse from blood into tissues and vice versa from tissues into bl ood. We used an in vivo model of intestinal ischemia (superior mesenteric a rtery occlusion) selectively increasing NO levels in intestinal tissue and an infusion of L-arginine selectively increasing NO levels in blood. In thi s model we followed formation of nitrosyl complexes of hemoglobin (Hb-NO) i n blood and nitrosyl-diethyldithiocarbamate-iron complexes (DETC-Fe-NO) in ischemic intestine and normoxic tissues by means of electron paramagnetic r esonance spectroscopy. NO trapping by DETC-Fe in the tissues resulted in a reduction of I-Ib-NO levels in blood accompanied by the formation of water- insoluble DETC-Fe-NO complexes in ischemic intestine and normoxic tissues b oth during ischemia and during reperfusion, Administration of L-arginine in creased NO levels in blood but neither in ischemic intestine nor in normoxi c tissue. Our data suggest that NO released in blood from endothelial cells does not diffuse into tissue. In contrast, NO formed in tissue diffuses in to blood. The latter indicates that NO formed in tissues may exert its biol ogical activities systematically. (C) 2001 Elsevier Science B.V. All rights reserved.