Phosphate, the forgotten mineral in hypertension

Abstract

Purpose of review: To review the current literature related to the role of inorganic phosphate (Pi) in the pathogenesis of hypertension Recent findings: An increasing number of publications has revealed a detrimental role of inorganic Pi, which is commonly used as a flavor enhancer or preservative in the processed food, in promoting hypertension in otherwise healthy individuals. Animal experimental data indicate that dietary Pi excess engages multiple mechanisms that promote hypertension, including overactivation of the sympathetic nervous system, increased vascular stiffness, impaired endothelium-dependent vasodilation, as well as increased renal sodium absorption or renal injury. These effects may be explained by direct effects of high extracellular Pi levels or increase in phosphaturic hormones such as fibroblast growth factor 23 (FGF23), or downregulation of klotho, a transmembrane protein expressed in multiple organs which possess anti-aging property. Summary: Dietary Pi, particularly inorganic Pi, is an emerging risk factor for hypertension which is ubiquitous in the western diet. Large randomized clinical trials are needed to determine if lowering dietary Pi content constitutes an effective nonpharmacologic intervention for prevention and treatment of hypertension.

Circadian rhythm of activin A and related parameters of mineral metabolism in normal and uremic rats

“…In more advanced CKD-MBD secondary hyperparathyroidism (sHPT), calcitriol deficiency, and hyperphosphatemia develop [31, 40, 46]. Elevated plasma P levels are associated with several deleterious endpoints in CKD patients including sHPT, arterial hypertension, extra-skeletal calcifications, cardiovascular disease, fracture rates, and all-cause mortality [13, 34, 55, 63]. Even in individuals with normal kidney function, plasma P levels are associated with long-term development of VC [16].…”

Hyperphosphatemia and its relationship with blood pressure, vasoconstriction, and endothelial cell dysfunction in hypertensive hemodialysis patients

“…Some of the proposed mechanisms to explain a relationship between phosphate and BP include increased arterial stiffness, increased renin–angiotensin–aldosterone system (RAAS) activity, and increased sympathetic nervous system (SNS) activity [ 11 , 12 , 16 , 17 ]. The negative consequences of increased arterial stiffness include increased central aortic BP (which can contribute to left ventricular hypertrophy) and widened pulse pressure (which can contribute to coronary hypoperfusion.)…”

“…Our study is novel in that we controlled for numerous demographic variables that have been associated with high pre-HD BP, we analyzed phosphate as a continuous variable, and we included analyses of vasoconstriction measurements and markers of ECD [9,15]. Some of the proposed mechanisms to explain a relationship between phosphate and BP include increased arterial stiffness, increased renin-angiotensin-aldosterone system (RAAS) activity, and increased sympathetic nervous system (SNS) activity [11,12,16,17]. The negative consequences of increased arterial stiffness include increased central aortic BP (which can contribute to left ventricular hypertrophy) and widened pulse pressure (which can contribute to coronary hypoperfusion.)…”

Phosphate Dysregulation and Metabolic Syndrome

“…Prolonged dietary phosphate overload could induce subclinical inflammatory responses to promote vascular stiffness, insulin resistance, and obesity, likely enhancing the likelihood of developing type 2 diabetes and cardiometabolic disorders [ 55 , 56 ] ( Figure 2 ). In ApoE knockout mice, high dietary phosphate intake accelerates atherogenesis independent of vascular calcification [ 57 ].…”