Dietary Phosphorus Acutely Impairs Endothelial Function

Abstract

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

Role of nutrient transporters in lifestyle-related diseases

“…Other studies, including our investigation, demonstrated that elevation of extracellular phosphate levels could induce endothelial dysfunction by an increase in oxidative stress and apoptosis, and a decrease in eNOS activity 48,49) . Inhibition of phosphate transport activity by phosphonoformic acid or siRNA can inhibit both calcification in vascular smooth muscle cells 44,50) and oxidative stress in endothelial cells 48,49) . Therefore, the phosphate transport activity of type III sodium-dependent phosphate transporters is important in the development of vascular complications leading to arteriosclerosis.…”

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

“…Furthermore, these data go along with biologic knowledge that both FGF-23 and ADMA interfere with the NO system and that inhibition of NO is a powerful mechanism prompting renal function loss in experimental models. Dietary phosphate load may itself induce endothelial dysfunction in experimental clinical studies in healthy humans, 31 whereas no such direct evidence exists for FGF-23. In the present study adjustment for serum phosphate or for a better indicator of phosphate burden (such as fractional phosphate excretion) did not modify the ADMA-FGF-23 interaction.…”

Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity

“…In vitro and in vivo experiments showed that a high phosphorus load acutely increases endothelial dysfunction by impairing vasodilation, raising the risk for cardiovascular disease. 67 High levels of serum phosphorus in healthy young adults have been associated with coronary atherosclerosis 68 and with left ventricular hypertrophy, 69 and high levels of serum phosphorus in a cohort study were associated with a 40% greater risk of heart failure. 70 A meta-analysis showed that serum phosphorus, but not serum calcium or PTH, was independently associated with mortality and risk for cardiovascular disease in CKD patients.…”