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Evaluation of Docosahexaenoic Acid in a Dog Model of Hypertension Induced Left Ventricular Hypertrophy
Authors:William C. Stanley  James W. Cox  Girma Asemu  Kelly A. O’Connell  Erinne R. Dabkowski  Wenhong Xu  Rogerio F. Ribeiro Jr  Kadambari C. Shekar  Stephen W. Hoag  Sharad Rastogi  Hani N. Sabbah  Caroline Daneault  Christine des Rosiers
Affiliation:1. Discipline of Physiology, University of Sydney, Anderson Stuart Building (F13), Sydney, NSW, 2006, Australia
2. Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA
3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA
4. Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, MI, USA
5. Department of Nutrition and Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada
Abstract:Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.
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