NITRIC-OXIDE MEDIATED, ENDOTHELIUM-DEPENDENT VASODILATION IS SELECTIVELY ATTENUATED IN THE POSTISCHEMIC EXTREMITY

Background. Attenuation of endothelium-dependent relaxing factor (EDRF ) release may contribute to adverse sequelae commonly seen after reper fusion of an acutely ischemic extremity. The purpose of this study was to identify the compound responsible for the EDRF activity in the ext remity and to evaluate its modulation by ischemia and reperfusion. Met hods. Isolated rat hindlimbs were perfused at constant pressure with a n albumin-enriched crystalloid buffer. Increasing log dose infusions o f acetylcholine,and nitroprusside were used to measure endothelium-dep endent (EDRF-mediated) and endothelium-independent vasoreactivity, res pectively. Results. Graded reductions in total vascular resistance wer e seen in response to both agonists in the control group (n = 11). In the postischemic group (n = 7), 60 minutes of normothermic ischemia an d 10 minutes of reperfusion reduced endothelium-dependent vasodilation to acetylcholine by approximately 40% (p < 0.01). Endothelium-indepen dent vasodilation to nitroprusside was unaffected. N(G)-monomethyl-L-a rginine (L-NMMA), a competitive inhibitor of nitric oxide release, att enuated vasodilation to acetylcholine (p < 0.01) but not nitroprusside in both control and postischemic groups. Conclusions. Endothelium-dep endent vasodilation in the rat hindlimb, mediated by nitric oxide, was selectively impaired by injury from ischemia and reperfusion. Strateg ies designed to minimize postischemic attenuation of nitric oxide rele ase may be beneficial in the management of acute limb ischemia.