Feedback

Long-Term Excessive Dietary Phosphate Intake Increases Arterial Blood Pressure, Activates the Renin–Angiotensin–Aldosterone System, and Stimulates Sympathetic Tone in Mice

Affiliation
Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria
Latic, Nejla;
ORCID
0000-0002-2472-675X
Affiliation
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, 01307 Dresden, Germany
Peitzsch, Mirko;
Affiliation
Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria
Zupcic, Ana;
ORCID
0000-0002-1610-1493
Affiliation
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, 01328 Dresden, Germany
Pietzsch, Jens;
ORCID
0000-0003-0801-6958
Affiliation
Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria
Erben, Reinhold G.

Increased dietary phosphate intake has been associated with severity of coronary artery disease, increased carotid intima–media thickness, left ventricular hypertrophy (LVH), and increased cardiovascular mortality and morbidity in individuals with normal renal function as well as in patients suffering from chronic kidney disease. However, the underlying mechanisms are still unclear. To further elucidate the cardiovascular sequelae of long-term elevated phosphate intake, we maintained male C57BL/6 mice on a calcium, phosphate, and lactose-enriched diet (CPD, 2% Ca, 1.25% P, 20% lactose) after weaning them for 14 months and compared them with age-matched male mice fed a normal mouse diet (ND, 1.0% Ca, 0.7% P). Notably, the CPD has a balanced calcium/phosphate ratio, allowing the effects of elevated dietary phosphate intake largely independent of changes in parathyroid hormone (PTH) to be investigated. In agreement with the rationale of this experiment, mice maintained on CPD for 14 months were characterized by unchanged serum PTH but showed elevated concentrations of circulating intact fibroblast growth factor-23 (FGF23) compared with mice on ND. Cardiovascular phenotyping did not provide evidence for LVH, as evidenced by unchanged LV chamber size, normal cardiomyocyte area, lack of fibrosis, and unchanged molecular markers of hypertrophy ( Bnp ) between the two groups. However, intra-arterial catheterization revealed increases in systolic pressure, mean arterial pressure, and pulse pressure in mice fed the CPD. Interestingly, chronically elevated dietary phosphate intake stimulated the renin–angiotensin–aldosterone system (RAAS) as evidenced by increased urinary aldosterone in animals fed the CPD, relative to the ND controls. Furthermore, the catecholamines epinephrine, norepinephrine, and dopamine as well as the catecholamine metabolites metanephrine. normetanephrine and methoxytyramine as measured by mass spectrometry were elevated in the urine of mice on CPD, relative to mice on the ND. These changes were partially reversed by switching 14-month-old mice on CPD back to ND for 2 weeks. In conclusion, our data suggest that excess dietary phosphate induces a rise in blood pressure independent of secondary hyperparathyroidism, and that this effect may be mediated through activation of the RAAS and stimulation of the sympathetic tone.

Cite

Citation style:
Could not load citation form.

Rights

License Holder: © 2022 by the authors.

Use and reproduction: