Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 8, Issue 4, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.118.010926
Keywords
hypertension; hypertrophy/remodeling; metabolic imaging; myocardial metabolism; rats
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Funding
- National Institutes of Health [R01 HL123627, R01 EB 001763, R01 HL128189, R01 HL61483]
- Department of Radiology and Medical Imaging at the University of Virginia
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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-[F-18] 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 monthold 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.
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