Vitamin D increases plasma renin activity independently of plasma Ca2+ via hypovolemia and β-adrenergic activity.
1, 25-Dihydroxycholechalciferol (calcitriol) and 19-nor-1, 25-dihydroxyvitamin D2 (paricalcitol) are vitamin D receptor (VDR) agonists. Previous data suggest VDR agonists may actually increase renin-angiotensin activity, and this has always been assumed to be mediated by hypercalcemia. We hypothesized that calcitriol and paricalcitol would increase plasma renin activity (PRA) independently of plasma Ca(2+) via hypercalciuria-mediated polyuria, hypovolemia, and subsequent increased β-adrenergic sympathetic activity. We found that both calcitriol and paricalcitol increased PRA threefold (P < 0.01). Calcitriol caused hypercalcemia, but paricalcitol did not. Both calcitriol and paricalcitol caused hypercalciuria (9- and 7-fold vs. control, P < 0.01) and polyuria (increasing 2.6- and 2.2-fold vs. control, P < 0.01). Paricalcitol increased renal calcium-sensing receptor (CaSR) expression, suggesting a potential cause of paricalcitol-mediated hypercalciuria and polyuria. Volume replacement completely normalized calcitriol-stimulated PRA and lowered plasma epinephrine by 43% (P < 0.05). β-Adrenergic blockade also normalized calcitriol-stimulated PRA. Cyclooxygenase-2 inhibition had no effect on calcitriol-stimulated PRA. Our data demonstrate that vitamin D increases PRA independently of plasma Ca(2+) via hypercalciuria, polyuria, hypovolemia, and increased β-adrenergic activity.
Dept. of Internal Medicine, Hypertension and Vascular Research Div., Henry Ford Hospital, 7121 E&R Bldg., 2799 W. Grand Blvd., Detroit, MI 48202. wbeierw1@hfhs.org.
Douglas K
DK
Atchison
Pamela
P
Harding
William H
WH
Beierwaltes
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D004872:Ergocalciferols / Q000494:pharmacology; D020896:Hypovolemia / Q000097:blood* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011141:Polyuria / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism* / Q000502:physiology; D012083:Renin / Q000096:biosynthesis / Q000097:blood*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D004872:Ergocalciferols; D011943:Receptors, Adrenergic, beta; C084656:paricalcitol; D012083:Renin; D002117:Calcitriol; D002118:Calcium
COX-2; PRA; PTH; calcitriol; calcium vitamin D; calcium-sensing receptor (CaSR); hypercalciuria; paricalcitol; polyuria; renin; sympathetic activity