Dietary Phosphate Reduces Hypertension, Inflammation and End Organ Damage

Abstract

Hypertension remains an increasing global health burden. Previous research has shown that dietary phosphate can modulate cardiovascular disease (CVD), yet the precise mechanism of how dietary phosphate contributes to blood pressure (BP), renal injury, and CVD remains unclear. Thus, we hypothesized that phosphate (P) reduces BP, inflammation, and end-organ damage. To this end, male C57bL/6 mice were either infused with four weeks of saline or Angiotensin II (490ng/kg/min) using a subcutaneous mini-osmotic pump. Over these 4 weeks, mice were fed a control diet for 2 weeks, followed by 2 weeks of phosphate-rich diet (0.15%, control (0.3%), and 1.5%P). Tail-cuff BP recordings were measured throughout the study protocol. To assess kidney damage, albumin in 24-hour urine samples, Masson’s trichrome staining, and DHE staining were performed. Flow cytometry was performed to examine immune cells infiltration in the kidney. Strikingly, our results show that control (0.3%P) and 1.5%P significantly reduced the SBP by 6.1 and 24.8 mmHg, respectively. In addition, CD4+T and CD8+T cell infiltration was dramatically reduced in the kidneys of the Angiotensin II-infused mice fed a 0.15%, control (0.3%P), 1.5%P diet compared to sham mice. Finally, Angiotensin II-infused mice fed a 0.15%, control (0.3%P), 1.5%P diet were protected from kidney glomerular damage, fibrosis, and ROS formation. We conclude that containing dietary phosphate mitigates hypertension and its end-organ damage.