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Elevation of superoxide in vascular smooth muscle cells restores oxyhemoglobin‐inhibited NO‐mediated vasodilation
Author(s) -
Yin ChiChao,
Xu Xin,
Hein Travis W,
Kuo Lih,
Huang KuangTse
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.a493-a
Subject(s) - vascular smooth muscle , vasodilation , nitric oxide , vasomotor , chemistry , superoxide , angiotensin ii , extracellular , medicine , endocrinology , pharmacology , biology , biochemistry , smooth muscle , receptor , enzyme
Previously, we have demonstrated that extracellular oxyhemoglobin (oxyHb) can reduce nitric oxide (NO) uptake by vascular smooth muscle cells (VSMCs). However, a small amount of superoxide (O 2 − ) in VSMCs can counteract the oxyHb effect and increase NO uptake for cGMP production. In the present study, we examined whether this phenomenon can be observed in an intact microvessel system for vasomotor regulation. Porcine coronary arterioles were isolated and pressurized for in vitro study. Intraluminal administration of 4‐μM oxyHb attenuated NO‐mediated vasodilation to serotonin. Extraluminal administration of a low concentration (0.1 nM) of angiotensin II (Ang II, 15 min incubation) did not alter resting vascular tone but selectively increased O 2 − in VSMCs. The serotonin‐induced vasodilation was restored in the presence of Ang II, and this reversal effect was abolished after treating vessels with O 2 − scavenger TEMPOL (0.1 mM). Similarly, pretreatment of Ang II increased VSMCs cGMP level in a co‐culture system in which endothelial cells were cultivated in the insert containing oxyHb and challenged with serotonin. The increased VSMC cGMP was abolished in the presence of TEMPOL. These results suggest that O 2 − in VSMCs can compete with lumenal oxyHb for cellular NO uptake and thus may play an important role in NO‐mediated vasomotor regulation when endogenous O 2 − level is moderately increased in VSMCs.