Polyunsaturated fatty acids treatment normalises the Na+/H+ exchanger hyperactivity and cardiac hypertrophy in spontaneously hypertensive rats.

ZAVALA, MAITE R.; LONGARZO, LUCRECIA; VÉLEZ RUEDA, OMAR; SABINA M. MATÉ; VILLA-ABRILLE MC.

Congreso; International Society for Heart Research (ISHR) Latin American Section; 2021

International Society for Heart Research (ISHR) Latin American Section

Several studies have shown that the consumption of polyunsaturated fatty acids of the omega-3 series (PUFA) is associated with a decrease in cardiovascular disease. PUFAs can affect membrane´s lipid composition, as well as proteins? location and/or function. The Na+/H+ exchanger (NHE1) is an integral membrane protein involved in maintenance of intracellular pH (pHi). Its activity is regulated by allosteric site sensitivity for H+, phosphorylation or by union of lipids or proteins in its cytoplasmic tail. The hyperactivity of NHE1 is associated with the development of various cardiac pathologies such as cardiac hypertrophy [1]. In spontaneously hypertensive rats (SHR) have been demonstrated the NHE1 hyperactivity [2], and additionally its inhibition reversed the hypertrophy of SHR.The aim of this project was evaluate the effect of early supplementing in diet with two major PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on the modulation of NHE1 activity and cardiac function in normo rats (Wistar, W) and spontaneous hypertensive (SHR).After weaning, the animals (male rats) received orally 200 mg/kg body mass/day of EPA and DHA for 3 months. Then we measured: systolic pressure (SP) and echocardiography parameters to calculated left ventricular mass index (LVMI), ejection fraction (EF%) and fractional shortening (FS%). The rats were sacrificed to isolate ventricular cardiomyocytes for measured the NHE1 activity.The SP was significantly greater in SHR compared to W (178±11 n=4 vs 123±6 n=7, p˂0,05). Although we did not find significant changes in systolic pressure in SHR rats after treatment (187±10 n=6,ns), we observed a significant reduction in LVMI expressed as mg/g (1,9±0,2 n=6 vs 2,6±0,2 n=4 p˂0,05).The NHE1 activity measured as the velocity of pHi recovery (dpHi/dt) after intracellular acidification (ammonium prepulse method), was significantly higher in SHR compared with W (0,115±0,004 n=5 vs 0,070±0,008 n=7, p˂0,05). NHE1 activity was not modified by the treatment with PUFA in W (0,060±0,004 n=10, ns vs W). However, NHE1 activity was significant decreased by PUFA in SHR, reaching values comparable with W (0,079±0,005 n=7, p˂0,05 vs SHR).These results allow us to suggest that a diet supplemented with PUFAs from an early age in SHR prevents the development of cardiac hypertrophy, probably by decreasing NHE1 activity, despite maintaining SP values (afterload).