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Hypercalcemia reduces plasma renin via parathyroid hormone, renal interstitial calcium, and the calcium-sensing receptor Atchison DK; Harding P; Beierwaltes WHHypertension 2011[Oct]; 58 (4): 604-10Acute 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.|Angiotensin I/pharmacology[MESH]|Animals[MESH]|Calcium Channels/genetics/metabolism[MESH]|Calcium/*metabolism[MESH]|Hypercalcemia/*metabolism[MESH]|Indans/pharmacology[MESH]|Kidney/*metabolism[MESH]|Male[MESH]|Models, Animal[MESH]|Parathyroid Hormone/*metabolism[MESH]|Parathyroidectomy[MESH]|Phenylpropionates/pharmacology[MESH]|RNA, Messenger/metabolism[MESH]|Rats[MESH]|Rats, Sprague-Dawley[MESH]|Receptors, Calcium-Sensing/antagonists & inhibitors/drug effects/*metabolism[MESH]|Renin/*blood[MESH]|Signal Transduction/drug effects/physiology[MESH]|TRPV Cation Channels/genetics/metabolism[MESH] |
