L-ARGININE TREATMENT ALTERS THE KINETICS OF NITRIC-OXIDE AND SUPEROXIDE RELEASE AND REDUCES ISCHEMIA REPERFUSION INJURY IN SKELETAL-MUSCLE/

Background Constitutive nitric oxide synthase (cNOS) may produce speci es involved in ischemia/reperfusion (IIR) injury: NO in the presence o f sufficient L-arginine and superoxide at the diminished local L-argin ine concentration accompanying IIR. Methods and Results During hindlim b I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porp hyrinic sensor), and L-arginine (chromatography), superoxide (chemilum inescence), and I/R injury were measured intermittently. Normal rabbit s were compared with those infused with L-arginine 4 mg.kg(-1).min(-1) for 1 hour. In both groups, approximate to 6 minutes into ischemia, a rapid increase of NO from its basal level of 50+/-17 to 115+/-7 mmol/ L, P<.005 (microvessels), was observed. In animals not treated with L- arginine, NO dropped below basal to undetectable levels (<1 nmol/L) du ring reperfusion. In animals treated with L-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperf usion (25 nmol/L). Decreased NO during IIR was accompanied by increase d superoxide, which during reperfusion reached 50 nmol/l, without or 2 3 nmol/L with L-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NA ME) during I/R. Conclusions L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protec tion from constriction (microvessel area, 17.77+/-0.95 Versus 11.66+/- 2.21 mu m(2) untreated, P<.0005) and reduction of edema after reperfus ion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P< .005).