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Testosterone stimulates peroxynitrite production in human coronary artery smooth muscle
Author(s) -
Puttabyatappa Yashoda,
White Richard
Publication year - 2008
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.22.1_supplement.742.10
Subject(s) - peroxynitrite , superoxide , nitric oxide , medicine , endocrinology , chemistry , vasodilation , vascular smooth muscle , vasoconstriction , testosterone (patch) , pharmacology , biochemistry , smooth muscle , enzyme
The increased incidence of cardiovascular disease in men compared with premenopausal women suggests an unfavorable effect of male sex hormone testosterone (T2) on the cardiovascular system. However, clinical and epidemiological studies report a controversial relationship between T2 and cardiovascular disease. Testosterone induces vasodilation, and this effect is thought to be mediated via nitric oxide. We now demonstrate that testosterone produces both nitric oxide (NO) and superoxide in human coronary artery smooth muscle cells (HCASMC). T2 stimulated NO‐dependent fluorescence in HCASMC, and this effect was attenuated by NOS inhibitors. T2‐stimulated superoxide production (measured by fluorescence and chemiluminescence) was inhibited by apocynin and sepiapterin. NO and superoxide react together to form peroxynitrite, and we have detected T2‐stimulated peroxynitrite production in HCASMC by employing the fluorescent dye DCF. Subsequent in vitro studies on porcine coronary artery support our findings. In conclusion, we hypothesize that testosterone stimulates production of peroxynitrite in vascular smooth muscle, and that peroxynitrite may mediate some of the effects of T2. (supported by HL080402)