Endothelial nitric oxide pathways in the pathophysiology of dengue: a prospective observational study.

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Title: Endothelial nitric oxide pathways in the pathophysiology of dengue: a prospective observational study.
Authors: Yacoub, S
Lam, PK
Huynh, TT
Nguyen Ho, HH
Dong Thi, HT
Van, NT
Lien, LT
Mongkolspaya, J
Culshaw, A
Yeo, TW
Wertheim, H
Simmons, C
Screaton, G
Wills, B
Item Type: Journal Article
Abstract: Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however the association of endothelial nitric oxide pathways with disease severity is unknown. Methods: We performed a prospective observational study in two Vietnamese hospitals, assessing patients presenting early (<72 hours fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperaemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability was evaluated using peripheral artery tonometry (EndoPAT) and plasma levels of L-arginine, Arginase-1 and ADMA were measured at serial time-points. The main outcome of interest was plasma leakage severity. Results: 314 patients were enrolled, median age of the participants was 21 (IQR 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness (OFI). Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs. 2.00, P<0.001), over acute time-points, apparent already in the early febrile phase (1.29 vs. 1.75, P=0.012). RHI correlated negatively with arginase-1, and positively with L-arginine (P=0.001). Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininaemia and high arginase-1 levels.
Issue Date: 29-Jun-2017
Date of Acceptance: 20-Jun-2017
ISSN: 1058-4838
Publisher: Oxford University Press (OUP)
Start Page: 1453
End Page: 1461
Journal / Book Title: Clinical Infectious Diseases
Volume: 65
Issue: 9
Copyright Statement: © 2017 The Author. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1093/cid/cix567
Sponsor/Funder: National Institute for Health Research
Commission of the European Communities
Wellcome Trust
Wellcome Trust
Wellcome Trust
GlaxoSmithKline Services Unlimited
Funder's Grant Number: N/A
Keywords: arginase
endothelial function
nitric oxide
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published online
Open Access location:
Appears in Collections:Department of Medicine
Faculty of Medicine

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