# Unraveling the mechanistic links between blood pressure regulation and calcium-magnesium homeostasis: Insights into hypertension, hyperparathyroidism, and mineral disorders

**Authors:** Pritha Dutta, Anita T. Layton, Toshio Matsumoto, Toshio Matsumoto, Toshio Matsumoto, Toshio Matsumoto

PMC · DOI: 10.1371/journal.pone.0341800 · 2026-02-04

## TL;DR

This study explores how blood pressure and calcium-magnesium balance are connected, using a model to understand conditions like hypertension and hyperparathyroidism.

## Contribution

A novel computational model integrating blood pressure and calcium-magnesium homeostasis in rats is developed and validated.

## Key findings

- Hypertension simulations show significant effects on PTH, calcitriol, and renal handling of Ca2+/Mg2+.
- Mg2+ deficiency was predicted to have a stronger effect on elevating mean arterial pressure than Ca2+ or vitamin D3 deficiencies.
- Primary hyperparathyroidism simulations predicted increased PTH, Ca2+, and calcitriol, leading to higher blood pressure and bone loss.

## Abstract

The systems regulating blood pressure and calcium-magnesium (Ca2+-Mg2+) homeostasis are increasingly recognized to have clinically relevant interactions, where alterations in one can lead to significant changes in the other. In this study, we developed a computational model integrating blood pressure regulation and Ca2+-Mg2+ homeostasis in a male rat. We simulated various conditions, including hypertension, Ca2+, Mg2+, and vitamin D3 deficiencies, and primary hyperparathyroidism. Simulations of hypertension, induced by various stimuli like increased renin or aldosterone secretion, demonstrated significant effects on parathyroid hormone (PTH), calcitriol, renal Ca2+/Mg2+ handling, and bone resorption. Dietary Ca2+, Mg2+, and vitamin D3 deficiencies was predicted to elevate mean arterial pressure, with Mg2+ deficiency having a stronger effect. Furthermore, the model predicted that primary hyperparathyroidism elevates PTH, Ca2+, and calcitriol, leading to increased mean arterial pressure and bone loss. Overall, this model provides valuable insights into the mechanistic links between blood pressure regulation and Ca2+-Mg2+ homeostasis, offering insights into clinical conditions like hypertension and hyperparathyroidism.

## Linked entities

- **Chemicals:** Ca2+ (PubChem CID 271), Mg2+ (PubChem CID 888), vitamin D3 (PubChem CID 5280795)
- **Diseases:** hyperparathyroidism (MONDO:0001741)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Slc12a1 (solute carrier family 12 member 1) [NCBI Gene 25065] {aka BSC1, Nkcc2}, Slc9a3 (solute carrier family 9 member A3) [NCBI Gene 24784] {aka Nhe3}, Ren (renin) [NCBI Gene 24715] {aka RATRENAA, RENAA, Ren1}, Agtr2 (angiotensin II receptor, type 2) [NCBI Gene 24182] {aka AT2-R, AT2R, AT<sub>2</sub>R}, Pthlh (parathyroid hormone-like hormone) [NCBI Gene 24695] {aka PLP}, AGTR1 (angiotensin II receptor type 1) [NCBI Gene 185] {aka AG2S, AGTR1B, AT1, AT1AR, AT1B, AT1BR}, Pth (parathyroid hormone) [NCBI Gene 24694] {aka PTH-(1-84), Pth1, Pthr1}, MROS (Melkersson-Rosenthal syndrome) [NCBI Gene 8011] {aka MRS}, Fdxr (ferredoxin reductase) [NCBI Gene 79122] {aka AR}, Casr (calcium-sensing receptor) [NCBI Gene 24247] {aka PCaR1, RaKCaR}, Tnfsf11 (TNF superfamily member 11) [NCBI Gene 117516] {aka ODF, OPGL, RANKL, TRANCE}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, Ace (angiotensin I converting enzyme) [NCBI Gene 24310] {aka CD143, Dcp1, StsRR92}, Agt (angiotensinogen) [NCBI Gene 24179] {aka ANRT, Ang, AngII, PAT}, Pth1r (parathyroid hormone 1 receptor) [NCBI Gene 56813] {aka PTHrel, Pthr, Pthr1}, Agtr1a (angiotensin II receptor, type 1a) [NCBI Gene 24180] {aka AT1, AT1A, AT1R, Agtr1}, Agtr1b (angiotensin II receptor, type 1b) [NCBI Gene 81638] {aka AT1, AT1B, AT3, AT<sub>1</sub>R, Agtr1}
- **Diseases:** Mg2+ deficiency (MESH:D007153), ALD (MESH:D000326), fracture (MESH:D050723), arrhythmias (MESH:D001145), hyper- and hypoparathyroidism (MESH:D007011), bone resorption (MESH:D001862), eclampsia (MESH:D004461), nephrocalcinosis (MESH:D009397), Primary hyperparathyroidism (MESH:D049950), myocardial hypertrophy (MESH:D006984), cardiovascular disease (MESH:D002318), heart failure (MESH:D006333), primary aldosteronism (OMIM:617027), calcium deficiency (MESH:D002128), Mineral (MESH:C537337), vitamin D3 (MESH:C564005), bone loss (MESH:D001847), Mineral Disorders (MESH:D012080), nephrolithiasis (MESH:D053040), osteoporosis (MESH:D010024), toxicity (MESH:D064420), Osteopenia (MESH:D001851), output (MESH:D002303), hypercalcemia (MESH:D006934), Vitamin D deficiency (MESH:D014808), ventricular remodeling (MESH:D020257), dietary Ca2+ (MESH:D000740), hypercalciuria (MESH:D053565), pre-eclampsia (MESH:D011225), Hypomagnesemia (OMIM:613882), Primary hyperaldosteronism (MESH:D006929), Hypertension (MESH:D006973), endocrine disorders (MESH:D004700), increase in cardiac output (MESH:D016534), Hyperparathyroidism (MESH:D006961)
- **Chemicals:** water (MESH:D014867), norepinephrine (MESH:D009638), Vitamin D (MESH:D014807), Aldosterone (MESH:D000450), cAMP (MESH:D000242), K+ (MESH:D011188), 1,25(OH)2D3 (MESH:D002117), 1,25(OH)2D (MESH:C097949), Na (MESH:D012964), -hydroxylated (-), Magnesium (MESH:D008274), D3 (MESH:D002762), Ca (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

50 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12872021/full.md

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Source: https://tomesphere.com/paper/PMC12872021