Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy.
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.
Discipline of Physiology, University of Sydney, Anderson Stuart Building (F13), Sydney, NSW, 2006, Australia. wstanley@usyd.edu.au.
William C
WC
Stanley
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
James W
JW
Cox
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
Girma
G
Asemu
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
Kelly A
KA
O'Connell
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
Erinne R
ER
Dabkowski
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
Wenhong
W
Xu
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
Eduardo
E
Hertel Ribeiro
Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA.
Kadambari C
KC
Shekar
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
Stephen W
SW
Hoag
Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, MI, USA.
Sharad
S
Rastogi
Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, MI, USA.
Hani N
HN
Sabbah
Department of Nutrition and Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
Caroline
C
Daneault
Department of Nutrition and Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
Christine
C
des Rosiers
D000450:Aldosterone; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000009:adverse effects*; D004285:Dogs; D005260:Female; D005355:Fibrosis; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*
D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D000450:Aldosterone