Acute activation of the calcium-sensing receptor inhibits plasma renin activity in vivo.
In vitro, the renin-secreting juxtaglomerular cells express the calcium-sensing receptor, and its activation with the calcimimetic cinacalcet inhibits renin release. To test whether the activation of calcium-sensing receptor similarly inhibits plasma renin activity (PRA) in vivo, we hypothesized that the calcium-sensing receptor is expressed in juxtaglomerular cells in vivo, and acutely administered cinacalcet would inhibit renin activity in anesthetized rats. Since cinacalcet inhibits parathyroid hormone, which may stimulate renin activity, we sought to determine whether cinacalcet inhibits renin activity by decreasing parathyroid hormone. Lastly, we hypothesized that chronically administered cinacalcet would inhibit basal and stimulated renin in conscious rats. Calcium-sensing receptors and renin were localized in the same juxtaglomerular cells using immunofluorescence in rat cortical slices fixed in vivo. Cinacalcet was administered acutely via intravenous bolus in anesthetized rats and chronically in conscious rats by oral gavage. Acute administration of cinacalcet decreased basal renin activity from 13.6 ± 2.4 to 6.1 ± 1.1 ng ANG I·ml(-1)·h(-1) (P < 0.001). Likewise, cinacalcet decreased furosemide-stimulated renin from 30.6 ± 2.3 to 21.3 ± 2.3 ng ANG I·ml(-1)·h(-1) (P < 0.001). In parathyroidectomized rats, cinacalcet decreased renin activity from 9.3 ± 1.3 to 5.2 ± 0.5 ng ANG I·ml(-1)·h(-1) (P < 0.05) similar to sham-operated controls (13.5 ± 2.2 to 6.6 ± 0.8 ng ANG I·ml(-1)·h(-1), P < 0.05). Chronic administration of cinacalcet over 7 days had no significant effect on PRA under basal or stimulated conditions. In conclusion, calcium-sensing receptors are expressed in juxtaglomerular cells in vivo, and acute activation of these receptors with cinacalcet inhibits PRA in anesthetized rats, independent of parathyroid hormone.
Atchison
Douglas K
DK
Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Ortiz-Capisano
M Cecilia
MC
Beierwaltes
William H
WH
D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000069449:Cinacalcet; D004232:Diuretics / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005665:Furosemide / Q000494:pharmacology; D007150:Immunohistochemistry; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D009281:Naphthalenes / Q000494:pharmacology*; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000819:agonists*; D012083:Renin / Q000097:blood*; D000092502:Renin Inhibitors
D000803:Angiotensin I; D002118:Calcium; D000069449:Cinacalcet; D004232:Diuretics; D005665:Furosemide; D009281:Naphthalenes; D044169:Receptors, Calcium-Sensing; D012083:Renin; D000092502:Renin Inhibitors