L-arginine treatment alters the kinetics of nitric oxide and superoxide release and reduces ischemia/reperfusion injury in skeletal muscle

The work of Dr Huk and his colleagues on how L-arginine treatment alters the kinetics of nitric oxide and the impact on skeletal muscle, published in Circulation, explains how ‘charging our bodies’ must be integrated into our daily lives.


Background: Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient l-arginine and superoxide at the diminished local l-arginine concentration accompanying I/R.

Methods and Results: During hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and l-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused with l-arginine 4 mg·kg−1·min−1 for 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 with l-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated with l-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 with l-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.

Conclusions: l-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 μm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56±2.13% versus 27.68±7.70% untreated, P<.005).

(Ihor Huk, Joseph Nanobashvili, Christoph Neumayer, Andreas Punz, Markus Mueller, Kaweh Afkhampour, Martina Mittlboeck, Udo Losert, Peter Polterauer, Erich Roth, Stephen Patton, and Tadeusz Malinski. Originally published 15 Jul 1997 https://doi.org/10.1161/01.CIR.96.2.667 Circulation. 1997;96:667–675)