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Dihydrotestosterone suppresses oxidative stress and improves vascular function following induction of inflammation in the cerebral circulation
Author(s) -
Gonzales Rayna,
Techapinyawat Rheana,
Zuloaga Kristen
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.685.14
Subject(s) - oxidative stress , dihydrotestosterone , inflammation , reactive oxygen species , medicine , endocrinology , nitric oxide , peroxynitrite , nitric oxide synthase , microglia , vascular smooth muscle , chemistry , superoxide , androgen , biochemistry , enzyme , smooth muscle , hormone
During pathophysiological events (i.e. stroke) enzymatic actions of cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase result in reactive oxygen species (ROS) generation that could potentially alter vascular function. Since dihydrotestosterone (DHT) augments COX‐2 in the absence of inflammation and attenuates COX‐2 in the presence of inflammation in rat and human vascular smooth muscle (VSM), we hypothesized that DHT would attenuate ROS and thus improve vascular function following an inflammatory insult. Oxidative stress was assessed in primary human brain VSM cells stimulated with cytokine in the absence or presence of DHT (18 h; 10 nM) using ROS‐indicator dyes (H 2 DCFDA and DAF‐FM). Myogenic tone was measured in middle cerebral arteries (MCA) isolated from castrated male rats treated with DHT (2 wk; 25 mg pellet/21 days) followed by endotoxin (6 h; 0.5 mg/ml i.p.). In VSM cells, DHT attenuated cytokine‐induced ROS production. In MCA, chronic DHT treatment increased pressure‐induced tone. However, in the presence of endotoxin, DHT's ability to increase tone was blunted without altering the myogenic response to step pressure increases. These data suggest that DHT may provide protection against inflammation‐induced injury in the cerebrovasculature in part by decreasing ROS (e.g. peroxynitrite and hydrogen peroxide) and thus improving vascular function. Sarver Heart Center & AHA (RG & KO)