Dietary omega-3 polyunsaturated fatty acids suppress NHE-1 upregulation in a rabbit model of volume- and pressure-overload

Background: Increased consumption of omega-3 polyunsaturated fatty acids (omega 3-PUFAs) from fish oil (FO) may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HE). The cardiac Na+/H+-exchanger (NHE-1) is a key mediator for these detrimental cardiac conditions. Consequently, chronic NHE-1 inhibition appears to be a promising pharmacological tool for prevention and treatment. Acute application of the FO omega 3-PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the NHE-1 in isolated cardiomyocytes. We studied the effects of a diet enriched with omega 3-PUFAs on the NHE-1 activity in healthy rabbits and in a rabbit model of HE induced by volume-and pressure-overload. Methods: Rabbits were allocated to four groups. The first two groups consisted of healthy rabbits, which were fed either a diet containing 1.25% (w/w) FO (omega 3-PUFAs), or 1.25% high-oleic sunflower oil (omega 9-MUFAs) as control. The second two groups were also allocated to either a diet containing omega 3-PUFAs or omega 9-MUFAs, but underwent volume- and pressure-overload to induce HE Ventricular myocytes were isolated by enzymatic dissociation and used for intracellular pH (pH(i)) and patch-clamp measurements. NHE-1 activity was measured in HEPES-buffered conditions as recovery rate from acidosis due to ammonium prepulses. Results: In healthy rabbits, NHE-1 activity in omega 9-MUFAs and omega 3-PUFAs myocytes was not significantly different. Volume- and pressure-overload in rabbits increased the NHE-1 activity in omega 9-MUFAs myocytes, but not in omega 3-PUFAs myocytes, resulting in a significantly lower NHE-1 activity in myocytes of omega 3-PUFA fed HE rabbits. The susceptibility to induced delayed afterdepolarizations (DADs), a cellular mechanism of arrhythmias, was lower in myocytes of HE animals fed o3-PUFAs compared to myocytes of HE animals fed omega 9-MUFAs. In our rabbit HE model, the degree of hypertrophy was similar in the omega 3-PUFAs group compared to the omega 9-MUFAs group. Conclusion: Dietary omega 3-PUFAs from FO suppress upregulation of the NHE-1 activity and lower the incidence of DADs in our rabbit model of volume- and pressure-overload.