l-Arginine Treatment Alters the Kinetics of Nitric Oxide and Superoxide Release and Reduces Ischemia/Reperfusion Injury in Skeletal Muscle

• DOI: 10.1161/01.cir.96.2.667
• Publication Date: 2012-06-12T00:41:02Z
• Authors: Igor Huk; Joseph Nanobashvili; Christoph Neumayer; Andreas Punz; Markus Mueller; Kaweh Afkhampour; Martina Mittlboeck; Udo Losert; Peter Polterauer; Erich Roth; Stephen Patton; Tadeusz Malinski
• Keywords: Male; 0301 basic medicine; Kinetics; 03 medical and health sciences; 0302 clinical medicine; Superoxides; Reperfusion Injury; Animals; Rabbits; Arginine; Muscle, Skeletal; Nitric Oxide; 3. Good health

BackgroundConstitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficientl-arginine and superoxide at the diminished locall-arginine concentration accompanying I/R.Methods and ResultsDuring hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), andl-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused withl-arginine 4 mg·kg−1·min−1for 1 hour. In both groups, ≈6 minutes into ischemia, a rapid increase of NO from its basal level of 50±17 to 115±7 nmol/L,P<.005 (microvessels), was observed. In animals not treated withl-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated withl-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperfusion (25 nmol/L). Decreased NO during I/R was accompanied by increased superoxide, which during reperfusion reached 50 nmol/L without or 23 nmol/L withl-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NAME) during I/R.Conclusionsl-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77±0.95 versus 11.66±2.21 μm2untreated,P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56±2.13% versus 27.68±7.70% untreated,P<.005).