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Superoxide anion is generated selectively by endothelin‐1 in resistance vessels and enhances their contractility
Author(s) -
Wang Dan,
Wilcox Christopher S
Publication year - 2007
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.21.5.a444-d
Subject(s) - myograph , superoxide , chemistry , vasoconstriction , contractility , phenylephrine , contraction (grammar) , medicine , reactive oxygen species , endocrinology , angiotensin ii , pharmacology , biochemistry , receptor , blood pressure , enzyme
Reactive oxygen spice (ROS) and endothelin‐1 (ET‐1) contribute to angiotensin‐induced hypertension. We used isolated mesenteric resistance arteries (MRAs) from EC‐SOD knockout (−/ −) mice (n=10) and EC‐SOD wild type (+/+) mice (n=10), as a model to investigate the hypothesis that microvascular ET‐1 and superoxide anion (O 2 .− ) interact to enhance contractility. Tension and O 2 .− were quantitated in real time in dihydroethidium (DHE)‐ loaded MRAs in a myograph equipped with a dual‐emission photon detection fluorescence system to measure ethidium (Eth):DHE ratio (E/D) as a direct readout of O 2 .− activity. Phenylephrine‐induced contractions were similar in MRAs from both groups and did not change E/D ratio. However, ET‐1 induced contractions were significantly increased in −/ − mice (100±3% vs 66±5%, p<0.01) and were accompanied by a selective increased in E/D ratio only in ECSOD−/− mice (3.7±0.5 vs 0.5±0.8, p<0.01). PEG‐SOD normalized augmented ET‐1 contraction (64 ± 4% vs 71 ± 3%; p=ns) and prevent an increase in E/D ratio in MRAs from −/− (0.6±0.5 vs 0.5 ±0.8, p=ns). In summary, ET‐1 generates microvascular O 2 .− that enhances its vasoconstrictive action. This is normally prevented by vascular metabolism of O 2 .− by EC‐SOD which therefore emerges as a major microvascular defense against ROS and vasoconstriction and a potential therapeutically target.