Open AccessMetabolic Changes in Spontaneously Hypertensive Rat Hearts Precede Cardiac Dysfunction and Left Ventricular Hypertrophy
Author(s) -
Li Jie,
Kemp Brandon A.,
Howell Nancy L.,
Massey James,
Mińczuk Krzysztof,
Huang Qiao,
Chordia Mahendra D.,
Roy R. Jack,
Patrie James T.,
Davogustto Giovanni E.,
Kramer Christopher M.,
Epstein Frederick H.,
Carey Robert M.,
Taegtmeyer Heinrich,
Keller Susanna R.,
Kundu Bijoy K.
Publication year - 2019
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.118.010926
Subject(s) - medicine , endocrinology , pressure overload , ejection fraction , muscle hypertrophy , metabolite , glucose uptake , left ventricular hypertrophy , oxidative stress , endoplasmic reticulum , in vivo , blood pressure , cardiology , cardiac hypertrophy , heart failure , insulin , chemistry , biology , biochemistry , microbiology and biotechnology
Background Sustained pressure overload leads to changes in cardiac metabolism, function, and structure. Both time course and causal relationships between these changes are not fully understood. Therefore, we studied spontaneously hypertensive rats (SHR) during early hypertension development and compared them to control Wistar Kyoto rats. Methods and Results We serially evaluated myocardial glucose uptake rates (Ki) with dynamic 2‐[ 18 F] fluoro‐2‐deoxy‐D‐glucose positron emission tomography, and ejection fraction and left ventricular mass to body weight ratios with cardiac magnetic resonance imaging in vivo, determined glucose uptake and oxidation rates in isolated perfused hearts, and analyzed metabolites, mammalian target of rapamycin activity and endoplasmic reticulum stress in dissected hearts. When compared with Wistar Kyoto rats, SHR demonstrated increased glucose uptake rates (Ki) in vivo, and reduced ejection fraction as early as 2 months of age when hypertension was established. Isolated perfused SHR hearts showed increased glucose uptake and oxidation rates starting at 1 month. Cardiac metabolite analysis at 2 months of age revealed elevated pyruvate, fatty acyl‐ and branched chain amino acid‐derived carnitines, oxidative stress, and inflammation. Mammalian target of rapamycin activity increased in SHR beginning at 2 months. Left ventricular mass to body weight ratios and endoplasmic reticulum stress were elevated in 5 month‐old SHR. Conclusions Thus, in a genetic hypertension model, chronic cardiac pressure overload promptly leads to increased myocardial glucose uptake and oxidation, and to metabolite abnormalities. These coincide with, or precede, cardiac dysfunction while left ventricular hypertrophy develops only later. Myocardial metabolic changes may thus serve as early diagnostic markers for hypertension‐induced left ventricular hypertrophy.