Molecular Mechanisms by which Phosphate Modulates Angiotensin II-Induced Hypertension

Abstract

Hypertension or high blood pressure is a critical health burden. Adherence to certain diets lowers the risk of hypertension. Preliminary data have shown a significant decrease in BP in mice receiving high dietary phosphate. High dietary phosphate stimulates the release of FGF23 from bones, and binds to its renal FGFR, causing downregulation in the expression of sodium-phosphate-dependent cotransporters (NaPIIa/c) located at the level of proximal convoluted tubules and encoded by SLC34A1/3 respectively, thus contributing to a decrease in the reuptake of phosphate coupled with sodium ion and increased excretion in urine. Our aim is to investigate the underlying mechanisms by which phosphate modulates hypertension by influencing the activity of these transporters. Initially, hypertension was induced by infusing male mice with Ang II pumps subcutaneously and fed low: 0.15% P, Control: 0.3%, High: 1.5% P. Mice were sacrificed, and kidneys were harvested to determine mRNA expression levels of FGF23 and SLC34A1-3. Urine and plasma phosphorous were analyzed. To assess the effect of phosphate on renal damage, DHE stain for ROS and NGAL were done. Our results showed that in hypertensive mice fed high dietary phosphate there was an alteration in FGF23 and downregulation in SLC34A1-3, and changes in urine phosphate excretion with variation in plasma phosphate. In addition, ROS was found in all groups of hypertensive mice and NGAL was increased in hypertensive mice receiving a high dietary group. Dietary phosphate might be used as a non-pharmacological intervention in the prevention and control of hypertension, however, further investigations into phosphate regulatory mechanisms and its effect on kidney damage should be assessed.