Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women
Open Access
- 1 March 2012
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 302 (5), H1211-H1218
- https://doi.org/10.1152/ajpheart.01065.2011
Abstract
The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH4), a critical cofactor for endothelial nitric oxide synthase to produce nitric oxide, would increase vascular endothelial-dependent vasodilatory tone and decrease arterial stiffness in estrogen-deficient postmenopausal women. Additionally, we examined whether the beneficial effects of estrogen on vascular function were possibly related to BH4. Arterial stiffness (carotid artery compliance) and endothelial-dependent vasodilation [brachial artery flow-mediated dilation (FMD)] were measured in postmenopausal ( n = 24; 57 ± 1 yr, mean ± SE) and eumenorrheic premenopausal ( n = 9; 33 ± 2 yr) women before and 3 h after the oral administration of BH4. Subsequently, in postmenopausal women, vascular testing (before and after BH4) was repeated following randomization to either 2 days of transdermal estradiol or placebo. Baseline carotid artery compliance and brachial artery FMD were lower in postmenopausal than in premenopausal women ( P < 0.0001). BH4administration increased carotid artery compliance (0.61 ± 0.05 to 0.73 ± 0.04 mm2·mmHg−1·10−1vs. baseline, P < 0.0001) and brachial artery FMD ( P < 0.001) in postmenopausal women but had no effect in premenopausal women ( P = 0.62). Carotid artery compliance (0.59 ± 0.05 to 0.78 ± 0.06 mm2·mmHg−1·10−1, P < 0.001) and FMD increased in postmenopausal women in response to estradiol ( P = 0.02) but were not further improved with the coadministration of BH4, possibly because estrogen increased BH4bioavailability. Carotid artery compliance and FMD increased with BH4in the placebo group ( P = 0.02). Although speculative, these results suggest that reduced vascular BH4may be an important contributor to arterial stiffening in estrogen-deficient postmenopausal women, related in part to reduced endothelial-dependent vasodilatory tone.Keywords
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