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eNOS‐derived NO promotes microvascular hyperpermeability in ischemia‐reperfusion (I‐R) njury
Author(s) -
Kanetaka Takehito,
Duran Ricardo G,
Lal Brajesh K,
Pappas Peter J,
Duran Walter N
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1151-c
Subject(s) - enos , cremaster muscle , chemistry , ischemia , medicine , endocrinology , microcirculation , vasodilation , nitric oxide , nitric oxide synthase
The role of NO in I‐R injury is controversial. We tested the hypothesis that eNOS‐derived NO plays a significant role in microvascular hyperpermeability in I‐R. We induced ischemia for 2‐h in cremaster muscles of wild‐type (eNOS+/+) and eNOS −/− mouse knockout (KO) mice, and reperfused them for 1−h. We performed two experimental protocols. 1) We evaluated integrated optical intensity (IOI, an index of permeability) of FITC‐dextran‐70 kDa by digital image analysis. I‐R increased net peak IOI significantly in wild‐type muscle (2 ± 1 to 68.5 ± 21.3 units; mean ± SE), while I‐R impact on permeability was reduced in muscles of KO mice (2 ± 1 vs. 16.4 ± 3.1 units). 2) We measured NO concentration with a NO‐electrode near arterioles (40–50 μm diameter). We administered ACh (10 μM, 5‐min) topically to the cremaster before and after I‐R period. Interestingly, ACh stimulated similar periarteriolar net NO production in cremaster of eNOS+/+ (baseline 246 ± 116 to 502 ± 235 nM; p<0.05, paired t‐test) and eNOS −/ − mice (baseline 341 ± 228 to 619 ± 354 nM; p<0.05). ACh‐stimulated NO production was reduced after I‐R in wild‐type and KO mice (372 ± 193 to 451 ± 188; 187 ± 61 to 240 ± 72 nM, respectively; p<0.05). Our data support the hypothesis that eNOS‐ derived NO plays an important role in microvascular hyperpermeability in I‐R. We also demonstrate that ACh stimulates NO production from other NOS isoforms in mouse cremaster muscle (supported by 5RO1 HL70634).