Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart
Author(s)
Type
Journal Article
Abstract
Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I‐supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l−1 NaCl (as control) or 0.7 mmol l−1 NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate‐supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l‐arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics.
Date Issued
2014-11-01
Date Acceptance
2014-08-18
Citation
JOURNAL OF PHYSIOLOGY-LONDON, 2014, 592 (21), pp.4715-4731
ISSN
0022-3751
Publisher
Wiley
Start Page
4715
End Page
4731
Journal / Book Title
JOURNAL OF PHYSIOLOGY-LONDON
Volume
592
Issue
21
Copyright Statement
© 2014 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society
This is an open access article under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000344650800010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Physiology
Neurosciences & Neurology
HIGH-ALTITUDE HYPOXIA
OBSTRUCTIVE PULMONARY-DISEASE
NITRIC-OXIDE
SKELETAL-MUSCLE
METABOLIC ADAPTATION
ENERGY-METABOLISM
INORGANIC NITRATE
S-NITROSATION
BLOOD-FLOW
MECHANISMS
Publication Status
Published
Date Publish Online
2014-08-27