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Age‐ and estrogen‐dependent effects on cerebrovascular reactivity: shifting from beneficial to detrimental (1069.6)
Author(s) -
Deer Rachel,
Perkins Lisa,
Stallone John
Publication year - 2014
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.28.1_supplement.1069.6
Subject(s) - estrogen , medicine , endocrinology , reactivity (psychology) , vasoconstriction , chemistry , radioimmunoassay , pathology , alternative medicine
Although mechanisms underlying the beneficial effects of estrogen on cerebrovascular (CV) function are well known, the age‐dependent deleterious effects are largely unknown. We hypothesized that age enhances the deleterious effects of estrogen on CV function by altering the role of prostanoids in modulating CV reactivity. Female (F) rats approximating key stages of hormonal aging were studied: pre‐menopausal (mature multigravid, MA), and post‐menopausal (reproductively senescent, RS). Rats underwent bilateral ovariectomy (O); some received estrogen replacement therapy (OE). Reactivity to VP (10‐12‐10‐7M) was measured in pressurized middle cerebral arteries (%vasoconstriction) using COX‐1 (SC560, SC, 1μM) or COX‐2 (NS398, NS, 10μM) selective inhibitors. Maximal VP reactivity in MAO (64±0.7%) was attenuated in MAOE by 21%; in contrast, reactivity in RSO (59±1.1%) was enhanced in RSOE by 27%. In MAO and RSO, SC and NS reduced reactivity similarly. In MAOE, SC reduced reactivity to a greater extent than NS (Δ59% vs Δ34%); however, in RSOE this effect was reversed (Δ65% NS vs Δ36% SC). VP‐stimulated release of PGI2 and TXA2 (radioimmunoassay of 6‐keto‐PGF1α and TxB2, stable metabolites, pg/mg dry wt/45min) in MAO (22,805 ± 3,108) and RSO (18,499±1,563) was increased by estrogen in MAOE (+58%) and RSOE (+56%). In contrast, PGI2 in MAO (22,805±3,108) and MAOE (35,975±2,133) was reduced by age in both RSO (‐19%) and RSOE (‐20%). VP‐stimulated TXA2 in MAO (671±57) and RSO (527±71) was increased by estrogen in MAOE (+62%) and RSOE (+165%). TXA2 in MAOE (1,085±70) was increased by age in RSOE (+21%) with no difference in MAO and RSO. These data reveal that the vascular effects of estrogen are distinctly age‐dependent. In younger F, beneficial effects of estrogen are evident (decreased vasoconstriction, increased dilator function). Conversely, in older F, detrimental effects of estrogen dominate (enhanced vasoconstriction, increased constrictor prostanoid function). Grant Funding Source : NIH: HL‐080402