van Borren Marcel M G J, den Ruijter Hester M, Baartscheer Antonius, Ravesloot Jan H, Coronel Ruben, Verkerk Arie O
Heart Failure Research Center, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
Front Physiol. 2012 Apr 2;3:76. doi: 10.3389/fphys.2012.00076. eCollection 2012.
Increased consumption of omega-3 polyunsaturated fatty acids (ω3-PUFAs) from fish oil (FO) may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HF). 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 ω3-PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the NHE-1 in isolated cardiomyocytes. We studied the effects of a diet enriched with ω3-PUFAs on the NHE-1 activity in healthy rabbits and in a rabbit model of HF induced by volume- and pressure-overload.
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 (ω3-PUFAs), or 1.25% high-oleic sunflower oil (ω9-MUFAs) as control. The second two groups were also allocated to either a diet containing ω3-PUFAs or ω9-MUFAs, but underwent volume- and pressure-overload to induce HF. 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.
In healthy rabbits, NHE-1 activity in ω9-MUFAs and ω3-PUFAs myocytes was not significantly different. Volume- and pressure-overload in rabbits increased the NHE-1 activity in ω9-MUFAs myocytes, but not in ω3-PUFAs myocytes, resulting in a significantly lower NHE-1 activity in myocytes of ω3-PUFA fed HF rabbits. The susceptibility to induced delayed afterdepolarizations (DADs), a cellular mechanism of arrhythmias, was lower in myocytes of HF animals fed ω3-PUFAs compared to myocytes of HF animals fed ω9-MUFAs. In our rabbit HF model, the degree of hypertrophy was similar in the ω3-PUFAs group compared to the ω9-MUFAs group.
Dietary ω3-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.
从鱼油（FO）中摄入更多的ω-3多不饱和脂肪酸（ω3-PUFAs）可能在缺血/再灌注、心肌肥厚和心力衰竭（HF）过程中具有心脏保护作用。心脏钠氢交换体（NHE-1）是这些有害心脏状况的关键介质。因此，长期抑制NHE-1似乎是一种有前景的预防和治疗药物工具。急性应用鱼油中的ω3-PUFAs二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）可抑制分离的心肌细胞中的NHE-1。我们研究了富含ω3-PUFAs的饮食对健康家兔以及容量和压力超负荷诱导的家兔HF模型中NHE-1活性的影响。
将家兔分为四组。前两组由健康家兔组成，分别喂食含1.25%（w/w）鱼油（ω3-PUFAs）的饮食或作为对照的1.25%高油酸葵花籽油（ω9-MUFAs）。后两组也分别喂食含ω3-PUFAs或ω9-MUFAs的饮食，但进行容量和压力超负荷以诱导HF。通过酶解分离心室肌细胞，并用于细胞内pH（pH(i)）和膜片钳测量。在HEPES缓冲条件下，以铵预脉冲引起的酸中毒恢复率来测量NHE-1活性。
在健康家兔中，ω9-MUFAs和ω3-PUFAs心肌细胞中的NHE-1活性无显著差异。家兔的容量和压力超负荷增加了ω9-MUFAs心肌细胞中的NHE-1活性，但未增加ω3-PUFAs心肌细胞中的NHE-1活性，导致喂食ω3-PUFAs的HF家兔心肌细胞中的NHE-1活性显著降低。与喂食ω9-MUFAs的HF动物的心肌细胞相比，喂食ω3-PUFAs的HF动物的心肌细胞对诱导的延迟后去极化（DADs，一种心律失常的细胞机制）的易感性较低。在我们的家兔HF模型中，ω3-PUFAs组与ω9-MUFAs组的肥厚程度相似。
在我们的容量和压力超负荷家兔模型中，来自鱼油的饮食ω3-PUFAs可抑制NHE-1活性的上调并降低DADs的发生率。
