Abstract W P232: High Sodium Diet Did Not Increase Peripheral Blood Pressure in a Transgenic Mouse Model of Alzheimer's Disease

Abstract

Introduction: The impairment of Ca2+ homeostasis has been connected to the deleterious effect of abnormal beta-amyloid (Ab) on the calcium sensing receptors (CaSR) in Alzheimer’s disease (AD). Elevated extracellular Ca2+ can also induce relaxation of arteries and prevent the development of hypertension. Change in ionic strength reduces the effect of CaSR agonists, such as Ab, and regulates Ca2+ homeostasis. Na+ gradient also increase ionic strength and may regulate Ca2+ homeostasis through CaSR and Na+/Ca2+ antiporter exchange to affect blood pressure. In non-pathological conditions, the elevation of Na+ gradient through high-sodium diet is considered as a reason for imbalance of Na+/Ca2+, and one of the several causes of hypertension and cardiovascular complications. However, the effect of Na+ gradient on AD patients is unclear. The purpose of this study was to test the hypothesis that in AD the increase of Na+ gradient diminishes the Ab ability on activation of CaSR and does not induce the hypertension. Method: We examined the effect of Na+ load on the arterial blood pressure in double transgenic mice harboring Ab precursor protein (APPswe), and presenilin-1 (PSEN1) as mouse model of AD (10-20 weeks, 25-30g). Wild type littermates were used as controls. Four groups: Control + low sodium diet (n=6); Control + high sodium diet (n=12); APP + low sodium diet (n=12); APP + high sodium diet (n=12) were tested for both systolic arterial blood pressure (SAP) and diastolic arterial blood pressure (DAP). Mice were fed a low- (0.08% NaCl) or a high-sodium (4% NaCl) diet for 3 months. Heart rate and SAP and DAP were measured noninvasively using tail blood pressure measurement device after 3 months. Results: Compared with mice fed standard diet (0.08% NaCl), mice fed high sodium diet showed markedly elevated SAP and DAP (134±4.8 compared with 162±2.8 mmHg, and 114±5.0 compared with 137±20 mmHg) (p<0.0001). There was no significant difference in both SAP and DAP between APP mice fed standard (0.08% NaCl) and high-sodium (4% NaCl) diet. SAP and DAP in elevated Aβ mouse were not affected by high dietary levels of sodium. Conclusion: Data from this AD model suggest that APP transgenic mice is resistant to high sodium-induced increase in systolic and diastolic blood pressure.