(Circulation. 1997;96:667-675.)
© 1997 American Heart Association, Inc.
Articles |
L-Arginine Treatment Alters the Kinetics of Nitric Oxide and Superoxide Release and Reduces Ischemia/Reperfusion Injury in Skeletal Muscle
From the Departments of Vascular Surgery, Surgical Research, Anatomy, Clinical Pharmacology, Computer Sciences, and Center of Biomedical Research, University of Vienna, Austria, and the Department of Chemistry and Institute of Biotechnology, Oakland University, Rochester, Mich (S.P., T.M.).
Correspondence to Tadeusz Malinski, PhD, Department of Chemistry and Institute of Biotechnology, Oakland University, Rochester, MI 48309-4401. E-mail malinski{at}ouchem.oakland.edu
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).
Key Words: ischemia • reperfusion • edema • free radicals • microcirculation
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