Abstract P312: High Potassium Intake Aggravates Cardiovascular Damage Accompanied By Premature Senescence In Hypertensive Apolipoproteine-ko Mice Under High Salt Diet

Abstract

Increased sodium intake aggravates cardiovascular diseases. Salt substitute containing potassium chlorideimproves cardiovascular outcome in hypertensive patients with high cardiovascular risk, however it isunknown whether it is attributed to potassium (K+) supplementation or sodium reduction. Here, weinvestigate the role of high K+ intake on the development of hypertensive cardiac damage in the presenceor absence of high salt diet. 8-10 weeks old apolipoproteinE-deficient mice (apoE-KO) were fed a normalK+ (0,55%) or high K+ (5%) diet throughout the experiment. Two weeks after diet start,mice were infusedwith angiotensin (Ang)II (500ng/kg/min) for 28 days. Cardiac function was assessed by MRI. High K+ dietincreased serum K+ levels compared to mice fed a normal K+ diet (5.3±1.2 vs. 3.9±0.4mmol/L, p<0.05).Interestingly, high K+ diet did not affect blood pressure or cardiac function. As expected, aldosteroneexcretion was increased in high K+ diet group compared to normal K+ diet (132±20 vs 8±18 ng/24h,p<0.01). To evaluate the consequence of K+ mediated aldosterone secretion for hypertensivecardiovascular damage, we additionally treated our high K+ group with high salt diet (1%NaCl) in thedrinking water. High K+ induced aldosterone production in the presence of high NaCl intake aggravatedhypertensive cardiac damage characterized by higher left ventricular mass, more cardiac fibrosis andinflammation compared to mice fed a high K+ or a high NaCl diet solely. Furthermore, the simultaneousintake of high K+/NaCl diet, induced higher mitochondrial ROS production in cardiac endothelial cellscompared to high K+ or high NaCl diet alone. As a consequence, cellular senescence markers such as p16and p21 were significantly higher in mice fed a high K+ / NaCl diet. Of note, co-treatment withspironolactone (50mg/kg/day), significantly attenuated cellular senescence and cardiovascular damage inmice fed a high K+/NaCl diet. High K+ diet compared to normal K+ diet does not have a beneficial effecton hypertensive cardiac damage in apoE-KO mice. Moreover, the present study indicates that potassium-induced aldosterone production aggravates the detrimental effect of high salt intake on cardiac health inhypertension by influencing cardiac senescence.