Affiliation:
1. 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.).
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).
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
158 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献