Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy

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.

Figure 1

Effects of treatment with DHA on the fatty-acyl content of myocardial phospholipids. †p<0.05 compared to the untreated group. ^ <0.05 compared to the placebo treated group.

Figure 2

Serum aldosterone concentration. *<0.05 compared to baseline within treatment group. #Compared to 8 weeks within treatment group. †p<0.05 compared to the untreated group at 8 weeks. There was a strong trend for high aldosterone concentration at 16 weeks with DHA treatment compare to placebo (p=0.064).

Figure 3

Arterial blood pressure measured by the tail cuff method plotted as a function of the duration of aldosterone infusion. *p<0.05 between placebo and DHA treated groups.

Figure 4

Echocardiographic assessment of left ventricular (LV) function taken at baseline before treatment (black bars) and after 15 weeks of treatment (open bars) with either placebo or DHA in dogs subjected to concurrent aldosterone-induced hypertension. E/A, peak rapid filling velocity (E)-to-peak atrial filling velocity (A) ratio. *p<0.05 compared to pretreatment within placebo or DHA treated groups.

Figure 5

The change in absorbance at 540 nm in SSM (upper panel) and IFM (Lower Panel) following addition of either 0.5 or 1.0 μmol Ca²⁺/mg mitochondrial protein. There were no significant differences between treatment groups.

Figure 6

Extramitochondrial Ca²⁺ concentration plotted as a function of cumulative Ca²⁺ load for SSM (upper panel) and IFM (Lower Panel) from the LV. There were no significant differences between treatment groups.