In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 2 ( 1997-07-15), p. 667-675
Abstract:
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 μm 2 untreated, P 〈 .0005) and reduction of edema after reperfusion (interfiber area, 16.56±2.13% versus 27.68±7.70% untreated, P 〈 .005).
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.96.2.667
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1997
detail.hit.zdb_id:
1466401-X
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