Cited by 173Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionBlood Pressure and Hypertension Studies

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Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals

Higashi, Y., Sasaki, S., Nakagawa, K., Fukuda, Y., Matsuura, H., Oshima, T., Chayama, K.·2002·American Journal of Hypertension

DOI 10.1016/s0895-7061(01)02317-2

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Abstract

BACKGROUND: A deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO synthesis and increases superoxide production. Supplementation of BH4 has been postulated to improve endothelial function in atherosclerotic patients. The purpose of this study was to determine whether BH4 restores endothelium-dependent vasodilation in patients with essential hypertension. METHODS: We evaluated the effects of BH4 on forearm vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, both in patients with essential hypertension and in age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using strain gauge plethysmography. RESULTS: The response of FBF to ACh was less in hypertensive patients (n = 8) than in normal control subjects (n = 8). There was no significant difference in FBF response to ISDN in the two groups. During coinfusion of BH4 (500 mg/min), the FBF response to ACh in hypertensive patients increased significantly (14.8 +/- 4.6 to 25.6 +/- 7.3 mL/min/100 mL tissue, P < .05) to the level of normal control subjects. In the control subjects, also, BH4 augmented the FBF response to ACh (27.8 +/- 8.7 to 36.1 +/- 9.6 mL/min/100 mL tissue, P < .05). The increase in FBF after ISDN was not altered by BH4 in either group (each group, n = 6). CONCLUSION: Supplementation of BH4 augments endothelium-dependent vasodilation in both normotensive and hypertensive individuals.

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Authors: Higashi, Y., Sasaki, S., Nakagawa, K., Fukuda, Y., Matsuura, H., Oshima, T., & Chayama, K.
Affiliations: Hiroshima University (JP)
Corresponding author: Higashi, Y.
ORCID: Higashi, Y.
Sasaki, S.
Fukuda, Y.
Matsuura, H.
Chayama, K.
Venue: American Journal of Hypertension
Publisher: Oxford University Press (OUP)
Published: 2002-04-01
Volume: 15
Issue: 4
Pages: 326-332
ISSN: 0895-7061 (ISSN-L)
1941-7225
DOI: 10.1016/s0895-7061(01)02317-2
OpenAlex: W2028671428
Cited by: 173
References: 31
Citations by year: 2025: 5 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 11 · 2012: 18
FWCI: 2.40
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Hypertension (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords: tetrahydrobiopterin, BH4 supplementation, endothelium-dependent vasodilation, acetylcholine, forearm blood flow, essential hypertension, isosorbide dinitrate, nitric oxide synthase cofactor, endothelial function, forearm circulation
MeSH terms: Acetylcholine, Adult, Biopterins, Drug Synergism, Endothelium, Vascular, Female, Forearm, Humans, Hypertension, Male, Middle Aged, Nitric Oxide, Regional Blood Flow, Nitric Oxide Synthase, Nitric Oxide Synthase Type III

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Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals

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