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Central injections of adeno‐associated virus‐siRNA gene to silence estrogen receptor beta (ERβ) augment aldosterone‐induced hypertension in female rats
Author(s) -
Xue Baojian,
BadauePassos Daniel,
Beltz Terry G,
Johnson Ralph F,
Johnson Alan Kim,
Hay Meredith
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.737.35
Subject(s) - endocrinology , small interfering rna , medicine , estrogen receptor , estrogen , estrogen receptor beta , estrogen receptor alpha , receptor , chemistry , rna , gene , cancer , breast cancer , biochemistry
Previous studies have shown that ovariectomy or central administration of a non‐selective estrogen receptor (ER) antagonist augments aldosterone (ALDO)‐induced hypertension in female rats. The present study further investigated which ER subtype is responsible for the protective effects of estrogen on ALDO‐induced hypertension. Aortic blood pressure was measured in female rats with the use of telemetry implants. ALDO (750 ng/h) was administered subcutaneously via an osmotic pump. At the same time, central injections of recombinant adeno‐associated virus (AAV) carrying small interference (si) RNA silencers of ERα (ERα‐siRNA), ERβ (ERβ‐siRNA) or scrambled siRNA (SCM‐siRNA) were used to knock down central ERα and ERβ subtypes. Both intracerebroventricular (icv) and paraventricular nucleus injections of AAV‐ERβ‐siRNA augmented ALDO‐induced hypertension (Δ25.4±0.6 mmHg, n=2 and Δ15.8±0.4 mmHg, n=3, respectively). However, rats with icv injections of ERα‐siRNA did not increase blood pressure induced by ALDO (Δ8.4±3.0 mmHg, n=2) in comparison to SCM‐siRNA rats (Δ9.2±2.2 mmHg, n=3). These data indicate that central ERβ mediates the protective effects of estrogen against ALDO‐induced hypertension. (Support: NIH HL‐59676 and HL‐62261)