{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:58:31Z","timestamp":1793041111159,"version":"4.5.0"},"reference-count":71,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p>In the present study, interactions of age and estrogen in the modulation of cerebrovascular function were examined in small arteries &lt;150 \u03bcM. The hypothesis tested was that age enhances deleterious effects of exogenous estrogen by augmenting constrictor prostanoid (CP)-potentiated reactivity of the female (F) cerebrovasculature. F Sprague-Dawley rats approximating key stages of \u201chormonal aging\u201d in humans were studied: perimenopausal (mature multi-gravid, MA, cyclic, 5\u20136 mo of age) and postmenopausal (reproductively senescent, RS, acyclic 10\u201312 mo of age). Rats underwent bilateral ovariectomy and were given estrogen replacement therapy (E) or placebo (O) for 14\u201321 days. Vasopressin reactivity (VP, 10<jats:sup>\u221212<\/jats:sup>\u201310<jats:sup>\u22127<\/jats:sup>M) was measured in pressurized middle cerebral artery segments, alone or in the presence of COX-1- (SC560, 1 \u03bcM) or COX-2- (NS398, 10 \u03bcM) selective inhibitors. VP-stimulated release of prostacyclin (PGI<jats:sub>2<\/jats:sub>) and thromboxane (TXA<jats:sub>2<\/jats:sub>) were assessed by radioimmunoassay of 6-keto-PGF<jats:sub>1\u03b1<\/jats:sub>and TXB<jats:sub>2<\/jats:sub>(stable metabolites). VP-induced vasoconstriction was attenuated in ovariectomized + estrogen-replaced, multigravid adult rats (5\u20136 mo; MAE) but potentiated in older ovariectomized + estrogen-replaced, reproductively senescent rats (12\u201314 mo; RSE). SC560 and NS398 reduced reactivity similarly in ovariectomized multigravid adult rats (5\u20136 mo; MAO) and ovariectomized reproductively senescent rat (12\u201314 mo; RSO). In MAE, reactivity to VP was reduced to a greater extent by SC560 than by NS398; however, in RSE, this effect was reversed. VP-stimulated PGI<jats:sub>2<\/jats:sub>was increased by estrogen, yet reduced by age. VP-stimulated TXA<jats:sub>2<\/jats:sub>was increased by estrogen and age in RSE but did not differ in MAO and RSO. Taken together, these data reveal that the vascular effects of estrogen are distinctly age-dependent in F rats. In younger MA, beneficial and protective effects of estrogen are evident (decreased vasoconstriction, increased dilator prostanoid function). Conversely, in older RS, detrimental effects of estrogen begin to be manifested (enhanced vasoconstriction and CP function). These findings may lead to age-specific estrogen replacement therapies that maximize beneficial and minimize detrimental effects of this hormone on small cerebral arteries that regulate blood flow.<\/jats:p><jats:p>Listen to this article's corresponding podcast at http:\/\/ajpheart.podbean.com\/e\/effects-of-age-and-estrogen-on-cerebrovascular-function\/ .<\/jats:p>","DOI":"10.1152\/ajpheart.00645.2015","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T04:16:30Z","timestamp":1458360990000},"page":"H1285-H1294","source":"Crossref","is-referenced-by-count":31,"title":["Effects of estrogen on cerebrovascular function: age-dependent shifts from beneficial to detrimental in small cerebral arteries of the rat"],"prefix":"10.1152","volume":"310","author":[{"given":"Rachel R.","family":"Deer","sequence":"first","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&amp;M University, College Station, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Stallone","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&amp;M University, College Station, Texas; and"},{"name":"Women's Health Division, Michael E. 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