Effects of resveratrol or estradiol on postexercise endothelial function in estrogen-deficient postmenopausal women

Abstract

Regular exercise enhances endothelial function in older men, but not consistently in estrogen-deficient postmenopausal women. Estradiol treatment improves basal endothelial function and restores improvements in endothelial function (flow-mediated dilation, FMD) to aerobic exercise training in postmenopausal women; however, estradiol treatment is controversial. Resveratrol, an estrogen receptor ligand, enhances exercise training effects on cardiovascular function and nitric oxide (NO) release in animal models, but impairs exercise training effects in men. We conducted a randomized cross-over, double-blinded, placebo-controlled pilot study to determine whether acute (single dose) resveratrol (250-mg tablet) or estradiol (0.05 mg/day transdermal patch) treatment enhances FMD at rest and after a single bout of moderate-intensity aerobic exercise in healthy estrogen-deficient postmenopausal women ( n = 15, 58.1 ± 3.2 yr). FMD was measured before and after (30, 60, and 120 min) a 40-min bout of moderate-intensity treadmill exercise (60–75% peak heart rate) under the respective conditions (separated by 1-2 wk). FMD was higher ( P < 0.05) before exercise and at all post-exercise time points in the resveratrol and estradiol conditions compared to placebo. FMD was increased from baseline by 120 min postexercise in the estradiol condition ( P < 0.001), but not resveratrol or PL conditions. Consistent with our previous findings, estradiol also enhances endothelial function in response to acute endurance exercise. Although resveratrol improved basal FMD, there was no apparent enhancement of FMD to acute exercise and, therefore, may not act as an estradiol mimetic. NEW & NOTEWORTHY The benefits of endurance exercise training on endothelial function are diminished in estrogen-deficient postmenopausal women, but estradiol treatment appears to restore improvements in endothelial function in this group. We show that basal endothelial function is enhanced with both acute estradiol and resveratrol treatments in estrogen-deficient postmenopausal women, but endothelial function is only enhanced following acute endurance exercise with estradiol treatment.

Targeting mitochondrial fitness as a strategy for healthy vascular aging

“…Incubation with resveratrol of arterial segments from older adults with hypertension and dyslipidemia improved EDD via a mechanism involving activation of eNOS and decreased oxidative stress, accompanied by enhanced mitochondrial antioxidant defense (increased MnSOD expression) [201]. Acute and/or chronic resveratrol supplementation improved endothelial function in healthy estrogen-deficient postmenopausal women [202] and middle-aged and older overweight/obese adults [203][204][205]. More recently, in glucose-intolerant older adults, 6 weeks of resveratrol supplementation improved reactive hyperemia, which is partly influenced by endothelial function, while also favorably modulating skeletal muscle mitochondria-related gene transcripts associated with mitochondrial dysfunction and oxidative phosphorylation and increasing mitochondrial number [206].…”

“…Role of sex differences: Potential sex differences in responsiveness to both lifestyle and pharmacological strategies must be determined [202,[250][251][252] and the role of vascular mitochondria in mediating sex differences should be established. Appropriate pre-clinical approaches and experiments and/or large, properly powered clinical trials are needed to accomplish this goal.…”

Exercise training and vascular function in postmenopausal individuals: a systematic review and meta-analysis

“…12,13 Pharmacological treatments including hormone therapy (HT) have shown promise in attenuating and improving FMD in postmenopausal individuals via reductions in oxidative stress. 14,15 However, the use of HT has also shown to be associated with an increased risk of cancer and CVD. [16][17][18][19] Equally, there is evidence to show no association with HT use and cancer risk.…”

“…This age-related decline in FMD becomes exaggerated for individuals around the timing of menopause onset and therefore elevates CVD risk 12,13 . Pharmacological treatments including hormone therapy (HT) have shown promise in attenuating and improving FMD in postmenopausal individuals via reductions in oxidative stress 14,15 . However, the use of HT has also shown to be associated with an increased risk of cancer and CVD 16-19 .…”

Serum ischemia-modified albumin level returns to its premenopausal level with 1-year hormone therapy in healthy menopausal women

“…The endothelium of elderly patients with multiple risk factors was more unresponsive to HT. Endothelial dysfunction with menopause improved with HT in healthy postmenopausal women; however, this effect was not observed in elderly women with multiple cardiovascular risk factors [ 11 ]. The negative effect of HT on endothelial functions was directly related to the time since menopause.…”