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Mechanism of Cardiovascular Mortality During Low Sodium Diet: NO Bioavailability And The Renin Angiotensin‐NADPH Oxidase System
Author(s) -
Suematsu Nobuhiro,
Ojaimi Caroline,
Kaminski Pawel M,
Wang Zipping,
Xu Xiaobin,
Wolin Michael S,
Recchia Fabio A,
Hintze Thomas H
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a524-c
Subject(s) - apocynin , chemistry , nadph oxidase , medicine , endocrinology , renin–angiotensin system , angiotensin ii , losartan , bradykinin , sodium , blood pressure , oxidative stress , receptor , organic chemistry
Adult male mongrel dogs were placed on low sodium diet (LS) which contains 0.5% sodium chloride for two weeks. Body weight (25±0.4kg to 24±0.4kg), left ventricular systolic pressure (137±3.4 to 124±6.7mmHg) and mean aortic pressure (MAP) (111±3.1 to 98±4.3 mmHg) decreased. Plasma angiotensin II concentration increased (4.4±0.7 to 14.8±3.7pg/ml), and losartan (10mg/kg) decreased MAP (95±4.7 to 52±4.1mmHg) in LS dogs. In LS heart tissues, lucigenin chemiluminescence was increased 2.3 fold to angiotensin II (10 −8 M) and bradykinin (10 −4 M) induced reduction of MVO 2 was decreased (−40±1.3 to −16±6.3%). These changes were completely restored by coincubation with tiron, tempol (10 −3 M each), or apocynin (10 −4 M). Veratrine (5μg/kg) induced NO‐dependent coronary vasodilation was inhibited by 44%, but the simultaneous intravenous infusion of ascorbic acid or apocynin completely reversed this inhibition. Switching of cardiac substrate uptake from free fatty acid (FFA) to glucose by the heart was observed (FFA; 8.97±1.39 to 4.53±1.12 μmol/min, Glucose; 1.31±0.52 to 6.86±1.78 μmol/min). Western blotting analysis showed that the protein expression of p47 phox was upregulated in the LS heart tissue. In conclusion, LS diet induces the activation of the renin‐angiotensin system which increases oxidative stress via the NADPH oxidase, and attenuates the NO bioavailability in the heart.