Document Detail

Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.
MedLine Citation:
PMID:  22245769     Owner:  NLM     Status:  MEDLINE    
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.
Kerrie L Moreau; Amie Meditz; Kevin D Deane; Wendy M Kohrt
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Publication Detail:
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:
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:
Created Date:  2012-02-24     Completed Date:  2012-04-19     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1211-8     Citation Subset:  IM    
Divisions of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
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MeSH Terms
Biopterin / administration & dosage,  analogs & derivatives*
Brachial Artery / drug effects,  physiology
Carotid Arteries / drug effects,  physiology
Endothelium, Vascular / drug effects*,  physiology
Estradiol / pharmacology
Estrogens / deficiency*
Middle Aged
Postmenopause / drug effects*,  physiology
Vascular Stiffness / drug effects*,  physiology
Vasodilator Agents / administration & dosage*
Grant Support
Reg. No./Substance:
0/Estrogens; 0/Vasodilator Agents; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 50-28-2/Estradiol
Comment In:
Rev Cardiovasc Med. 2012;13(4):e209-10   [PMID:  23470691 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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