Hypercalcemia Reduces Plasma Renin via Parathyroid Hormone, Renal Interstitial Calcium, and the Calcium-Sensing Receptor
Open accessAbstract
Acute hypercalcemia inhibits plasma renin activity (PRA). How this occurs is unknown. We hypothesized that acute hypercalcemia inhibits PRA via the calcium-sensing receptor because of parathyroid hormone-mediated increases in renal cortical interstitial calcium via TRPV5. To test our hypothesis, acute in vivo protocols were run in sodium-restricted, anesthetized rats. TRPV5 messenger RNA expression was measured with real-time quantitative RT-PCR. Acute hypercalcemia significantly decreased PRA by 37% from 32.0±3.3 to 20.3±2.6 ng of angiotensin I per milliliter per hour ( P <0.001). Acute hypercalcemia also significantly increased renal cortical interstitial calcium by 38% (1.73±0.06 mmol/L) compared with control values (1.25±0.05 mmol/L; P <0.001). PRA did not decrease in hypercalcemia in the presence of a calcium-sensing receptor antagonist, Ronacaleret (22.8±4.3 versus 21.6±3.6 ng of angiotensin I per milliliter per hour). Increasing plasma calcium did not decrease PRA in parathyroidectomized rats (22.5±2.6 versus 22.0±3.0 ng of angiotensin I per milliliter per hour). Parathyroidectomized rats were unable to increase their renal cortical interstitial calcium in response to hypercalcemia (1.01±0.11 mmol/L). Acutely replacing plasma parathyroid hormone levels did not modify the hypercalcemic inhibition of PRA in parathyroid-intact rats (39.1±10.9 versus 16.3±3.2 ng of angiotensin I per milliliter per hour; P <0.05). Renal cortical TRPV5 messenger RNA expression decreased by 67% in parathyroidectomized ( P <0.001) compared with intact rats. Our data suggest that acute hypercalcemia inhibits PRA via the calcium-sensing receptor because of parathyroid hormone–mediated increases in renal cortical interstitial calcium via TRPV5.
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Self-citation
- Authors
- Atchison, D. K., Harding, P., & Beierwaltes, W. H.
- Affiliations
- Wayne State University (US)
- Venue
- Hypertension
- Published
- 2011-10
- Volume
- 58
- Issue
- 4
- Pages
- 604-610
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3174336
- OpenAlex
- W2160204554
- Cited by
- 26
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wayne State University
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL090550)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK084654)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- hypercalcemia, plasma renin activity, calcium-sensing receptor, parathyroid hormone, TRPV5, renin-angiotensin system, parathyroidectomy, sodium restriction
- MeSH terms
- Angiotensin I, Animals, Calcium, Hypercalcemia, Indans, Kidney, Male, Parathyroid Hormone, Phenylpropionates, Renin, RNA, Messenger, Calcium Channels, Signal Transduction, Parathyroidectomy, Rats, Sprague-Dawley, Models, Animal, Receptors, Calcium-Sensing, TRPV Cation Channels, Rats
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