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 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.


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 x kg(-1) x min(-1) for 1 hour. In both groups, approximately 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 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).
Huk
I
I
Department of Vascular Surgery, Center of Biomedical Research, University of Vienna, Austria.
Nanobashvili
J
J
Neumayer
C
C
Punz
A
A
Mueller
M
M
Afkhampour
K
K
Mittlboeck
M
M
Losert
U
U
Polterauer
P
P
Roth
E
E
Patton
S
S
Malinski
T
T
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine