title: Hypercalcemia reduces plasma renin via parathyroid hormone, renal interstitial calcium, and the calcium-sensing receptor.
abstract: 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.
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Atchison
authors.forename: Pamela
authors.initials: P
authors.lastname: Harding
authors.forename: William H
authors.initials: WH
authors.lastname: Beierwaltes
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D006934:Hypercalcemia / Q000378:metabolism*; D007189:Indans / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D010281:Parathyroid Hormone / Q000378:metabolism*; D016105:Parathyroidectomy; D010666:Phenylpropionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D012083:Renin / Q000097:blood*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D007189:Indans; D010281:Parathyroid Hormone; D010666:Phenylpropionates; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; D000803:Angiotensin I; C561716:ronacaleret; D012083:Renin; D002118:Calcium