Interactions of age and estrogen in modulation of cerebrovascular function were examined in small arteries <150 μM. The hypothesis tested was that age enhances deleterious effects of exogenous estrogen by augmenting constrictor prostanoid (CP)-potentiated reactivity of female cerebrovasculature. Female Sprague-Dawley rats were studied: peri-menopausal (mature multigravid, MA, cyclic, 5-6 months age) and post-menopausal (reproductively senescent, RS, acyclic, 10-12 months age). Rats were ovariectomized and given estrogen (E) or placebo (O) for 14-21 days. Vasopressin reactivity (VP, 10-12 - 10-7M) was measured in pressurized middle cerebral artery segments, alone or in presence of COX-1- (SC560, 1 μM) or COX-2- (NS398, 10 μM) selective inhibitors. VP-stimulated prostacyclin (PGI2) and thromboxane (TXA2) release were assessed by radioimmunoassay. VP-induced vasoconstriction was attenuated in MAE but potentiated in older RSE. SC560 and NS398 reduced reactivity similarly in MAO and RSO. In MAE, VP reactivity was reduced to a greater extent by SC560 than by NS398; however, in RSE this effect was reversed. VP-stimulated PGI2 was increased by estrogen, yet reduced by age. VP-stimulated TXA2 was increased by estrogen and age in RSE, but did not differ in MAO and RSO. These data reveal that vascular effects of estrogen are distinctly age-dependent in female rats. In younger MA, beneficial and protective effects of estrogen are evident (decreased vasoconstriction, increased dilator prostanoids). In older RS, detrimental effects of estrogen are manifested (enhanced vasoconstriction and CPs). These findings may lead to age-specific estrogen replacement therapies that maximize beneficial and minimize detrimental effects on small cerebral arteries that regulate blood flow.
- middle cerebral artery
- Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology