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Chronic exposure to estradiol‐17 β (E2) causes hypertension in female rats: Role of IL‐1β and norepinephrine
Author(s) -
Subramanian Madhan,
Hamman D W,
Mohankumar S MJ,
Fink G D,
Mohankumar PS
Publication year - 2010
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.24.1_supplement.809.9
Subject(s) - endocrinology , medicine , norepinephrine , hypothalamus , cytokine , dopamine
Cardiovascular disease is the most prevalent cause for morbidity and mortality in women. Previous findings from our lab suggest that chronic exposure to low levels of E2 causes hypertension. The mechanisms underlying this effect are unknown. We believe that E2 affects central sites such as the Paraventricular nucleus (PVN) of the hypothalamus to cause hypertension, since the PVN plays a key role in the regulation of sympathetic activity. We hypothesized that chronic E2 exposure most probably increases cytokine levels in the PVN to affect norepinephrine (NE) levels leading to hypertension. To test this, 3–4 month old female Sprague Dawley rats were implanted s.c. with slow‐release E2 pellets. Animals were exposed to 20ng of E2/day for 30, 60 or 90 days (n=6). At the end of the treatment, animals were sacrificed and the PVN was microdissected and analyzed for NE and the cytokine, IL‐1β. Exposure to E2 produced a duration‐dependent increase in IL‐1β and NE levels. IL‐1β (pg/μg protein; mean±S.E.) was 19.4±1.2 after 30 days and increased significantly after 60 & 90 day exposure (34.1±5.9 & 24.9±3.0 respectively) compared to the control group 9.0±2.4 (p<0.05). Similarly NE values (pg/μg protein; mean±S.E.) were 5.01±1.04 after 30 days and increased significantly after 60 & 90 day exposure (53.8±12.4 & 78.9±14.5 respectively) compared to the control group (8.99± 3.23; p<0.05). The increase in IL‐1 β after chronic E2 exposure could stimulate NE release to increase sympathetic outflow contributing to hypertension. Supported by NIH AG027697.