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Decreased Telomerase Activity Converts the Mechanism of FMD from NO to H 2 O 2 in Human and Mouse Arterioles
Author(s) -
Beyer Andreas M.,
Gutterman David D.
Publication year - 2012
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.26.1_supplement.676.1
Subject(s) - catalase , dilator , reactive oxygen species , vasodilation , chemistry , telomerase , endocrinology , medicine , nitric oxide , endothelium , in vivo , oxidative stress , endothelial dysfunction , hydrogen peroxide , biology , biochemistry , genetics , gene
Reactive oxygen species (ROS) are important modulators of vascular reactivity. In disease, the mechanism of endothelium‐dependent vasodilation can shift from NO to hydrogen peroxide (H 2 O 2 ). Reduced telomerase activity (TA) has been linked to increased ROS production. Animals lacking telomerase develop hypertension but the underlying effects on the vasculature are unknown. We hypothesized that decreases in TA are associated with elevated ROS and a change in the mechanism of endothelium‐dependent dilation from NO to H 2 O 2. We postulate that this shift in dilator mechanism is conserved across species (mouse to human). Murine mesenteric arteries (~200 μm) were isolated and flow‐mediated dilation (FMD) was studied ex‐vivo (pressure gradient 0–100 cm H 2 O). Inhibition of TA shifted the mediator of FMD from NO to H 2 O 2 (% Max dilation at 100 cm H 2 O: Vehicle 72±9; +L‐NAME −8±8; +Catalase 92±6; TA inhibitor BIRB1532 10 μM 12–15 hours 84±7; +L‐NAME 81±10*; +Catalase −7±8* n≥4; * P <0.05 one way ANOVA vs. Vehicle). Resistance vessels (~200 μm) from the human adipose responded in a similar manner. Decreased TA shifted the mechanism of FMD from NO to H 2 O 2 (% Max dilation at 100 cm H 2 O: Vehicle 88±3; +L‐NAME −39±2; +Catalase 83±3; BIRB1532 88.7±6; +L‐NAME 85±2*; +Catalase 34±5* n≥3; * P <0.05 one way ANOVA vs. Vehicle). We conclude that telomerase may play a critical role in acute modulation of microvascular function across species.