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Reactive oxygen species contribute to augmented endothelin‐1 (ET‐1) vasoconstriction in intermittent hypoxia
Author(s) -
Kalra Roma,
Kanagy Nancy
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.20.4.a790-a
Subject(s) - vasoconstriction , tiron , mesenteric arteries , vasodilation , chemistry , medicine , endocrinology , catalase , reactive oxygen species , hypoxia (environmental) , artery , oxidative stress , oxygen , superoxide , biochemistry , organic chemistry , enzyme
We reported previously that simulating sleep apnea by exposing rats to intermittent hypoxia/hypercapnia (IH) during sleep increases arterial pressure, elevates plasma ET‐1, and augments vasoconstrictor sensitivity to ET‐1. Mesenteric arteries from IH rats also have increased reactive oxygen species (ROS) generation measured by lucigenin and administration of the antioxidant, tempol, prevents IH‐induced hypertension. Therefore we hypothesized that IH induced increases in vascular ROS generation augment ET‐1 vasoconstriction. To test this hypothesis, vasoconstrictor sensitivity to ET‐1 was examined in endothelium‐intact arteries from IH and Sham rats treated with the SOD mimetic tiron alone (10 μmol/L) or plus catalase (10 μmol/L). Tiron decreased the vasoconstrictor sensitivity to ET‐1 in Sham arteries but did not affect it in IH arteries (Sham = 90±1*, IH = 105±0.8, % control, * p ≤ 0.05). When catalase plus tiron was used to determine if H 2 O 2 mediated this inhibition, ET‐1constriction in IH arteries was not affected but constriction in Sham arteries was augmented (Sham = 140±5*, IH = 105±5 % control, * p ≤ 0.05). These data suggest that H 2 O 2 acts as a vasodilator in Sham arteries but in IH arteries, either (1) O 2 − production is diminished and therefore less H 2 O 2 is produced by tiron, or (2) arteries from IH rats are less sensitive to vasodilatory effects of H 2 O 2 and thus are not affected by either the tiron production of H 2 O 2 or catalase scavenging of H 2 O 2 . Because both in vivo and in vitro studies suggest ROS production is increased in IH arteries compared to Sham arteries, the increased vasoconstrictor effects of ET‐1 in IH rats may be due in part to decreased vascular sensitivity to H 2 O 2 dilation.