| Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. | |
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MedLine Citation:
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PMID: 22245769 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH(4)), 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 BH(4). 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 BH(4). Subsequently, in postmenopausal women, vascular testing (before and after BH(4)) 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). BH(4) administration increased carotid artery compliance (0.61 ± 0.05 to 0.73 ± 0.04 mm(2)·mmHg(-1)·10(-1) vs. 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 mm(2)·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 BH(4), possibly because estrogen increased BH(4) bioavailability. Carotid artery compliance and FMD increased with BH(4) in the placebo group (P = 0.02). Although speculative, these results suggest that reduced vascular BH(4) may be an important contributor to arterial stiffening in estrogen-deficient postmenopausal women, related in part to reduced endothelial-dependent vasodilatory tone. |
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Authors:
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Kerrie L Moreau; Amie Meditz; Kevin D Deane; Wendy M Kohrt |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-13 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 302 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-24 Completed Date: 2012-04-19 Revised Date: 2012-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1211-8 Citation Subset: IM |
Affiliation:
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Divisions of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Kerrie.Moreau@UCDenver.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biopterin
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administration & dosage,
analogs & derivatives* Brachial Artery / drug effects, physiology Carotid Arteries / drug effects, physiology Endothelium, Vascular / drug effects*, physiology Estradiol / pharmacology Estrogens / deficiency* Female Humans Middle Aged Postmenopause / drug effects*, physiology Vascular Stiffness / drug effects*, physiology Vasodilation* Vasodilator Agents / administration & dosage* |
| Grant Support | |
ID/Acronym/Agency:
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AG-027678/AG/NIA NIH HHS; RR-025780/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogens; 0/Vasodilator Agents; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 50-28-2/Estradiol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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