Trial reportAmerican journal of physiology. Heart and circulatory physiology2012
Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.
Trial report in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00608062 (Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency), which is not on this map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Relationship between lead exposure and different types of hypertension: systematic review and dose-response meta-analysis.Frontiers in public health · 2025Pooled it
- The acute effects of exercise intensity and inorganic nitrate supplementation on vascular health in females after menopause.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Trial
- A single dose of dietary nitrate supplementation protects against endothelial ischemia-reperfusion injury in early postmenopausal women.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2022Trial
- Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.The Journal of clinical endocrinology and metabolism · 2022Trial
- Effects of resveratrol or estradiol on postexercise endothelial function in estrogen-deficient postmenopausal women.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Trial
- Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aortic Stiffness in Patients With Rheumatoid Arthritis.Journal of the American Heart Association · 2016Trial
- Essential role of estrogen for improvements in vascular endothelial function with endurance exercise in postmenopausal women.The Journal of clinical endocrinology and metabolism · 2013Trial
- Tumor necrosis factor-α inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.Atherosclerosis · 2013Trial
- Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2013Trial
- Effects of dietary nitrate on cardiovascular reactivity in normotensive postmenopausal women.European journal of applied physiology · 2026Article
- Diet, the Gut Microbiome, and Estrogen Physiology: A Review in Menopausal Health and Interventions.Nutrients · 2026Review
- Genistein Restores Nitric Oxide Bioavailability and Attenuates Oxidative Stress in Angiotensin II-Induced Hypertensive Mice.Preventive nutrition and food science · 2026Article
- Impact of Testosterone on Endothelial Function Varies by GnRH Agonist Treatment.Journal of the Endocrine Society · 2025Article
- Does the Menstrual Phase Matter in Vascular Endothelial Responses to Acute Exercise? A Narrative Review of the Literature.Sports (Basel, Switzerland) · 2025Review
- Endothelial dysfunction in middle-aged and older men with low testosterone is associated with elevated circulating endothelin-1.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Short-term estradiol administration does not restore endothelin-B receptor-mediated vasodilation in postmenopausal women.American journal of physiology. Heart and circulatory physiology · 2025Article
- Higher amounts of habitual physical activity changes the relationship between hot flashes and subclinical cardiovascular disease risk.Physiological reports · 2025Article
- Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions.The journal of cardiovascular aging · 2025Article
- Role of BHAmerican journal of physiology. Heart and circulatory physiology · 2022Article
- Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.