Abstract 9887: Metformin Improves Metabolic, Functional, and Structural Abnormalities in Spontaneously Hypertensive Rat Hearts

• Published in: Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A9887-A9887
• Main Authors: Li, Jie, Minczuk, Krzysztof, Massey, James, Roy, Jack, Paul, Soumen, Patrie, James, Carey, Robert, Taegtmeyer, Heinrich, Keller, Susanna, Kundu, Bijoy
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.9887

IntroductionIn a chronic hypertension model [spontaneously hypertensive rats (SHR)], we observed profound myocardial metabolic changes during early hypertension, before or concomitant with cardiac dysfunction, and before left ventricular hypertrophy (LVH) developed.HypothesisEarly targeting of metabolic changes with metformin prevents contractile dysfunction and structural remodeling of SHR hearts in vivo.MethodsSHR and control Wistar-Kyoto (WKY) rats were treated with metformin (300 mg/kg/d in drinking water) starting at 2 months of age, when SHR hearts exhibit significant metabolic changes. The effect of metformin on cardiac metabolism, function and structure was assessed using dynamic FDG PET and CMR. FDG PET imaging quantified myocardial glucose uptake rates (Ki) while CMR analyzed ejection fraction (EF), left ventricular mass (LVM), and end-diastolic wall thickness (EDWT). Mean arterial pressure (MAP) was determined by carotid artery catheterization. Circulating free fatty acids (FFA) were measured, and heart mTOR activity was evaluated. Measurements were done at baseline (2 months) and after 3 months of treatment (at 5 months of age), when SHR develop LVH.ResultsMAP and glucose uptake rates were lower in treated (SHR+M) than in untreated SHR (p=0.022 and p=0.017, respectively). EF improved in treated SHR (p=0.009 vs. untreated SHR), and LVM/TL (tibia length) and EDWT were reduced (p=0.021 and p=0.002, respectively, vs. untreated SHR). Circulating FFA levels and myocardial mTOR activity (p-p70S6K) were reduced in treated SHR (p=0.047 and p=0.028, respectively, vs. untreated SHR).ConclusionsEarly metformin treatment reduces blood pressure, attenuates myocardial glucose uptake, and improves cardiac function in SHR. Metformin also reduces myocardial mTOR activity and prevents LVH in SHR hearts. Thus, metformin could serve as a novel pharmacologic agent to prevent or ameliorate chronic hypertension-induced LVH.