1. Vitamin D increases plasma renin activity independently of plasma Ca2+ via hypovolemia and β-adrenergic activity.
- Author
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Atchison DK, Harding P, and Beierwaltes WH
- Subjects
- Animals, Ergocalciferols pharmacology, Hypovolemia metabolism, Kidney metabolism, Male, Polyuria blood, Polyuria metabolism, Rats, Rats, Sprague-Dawley, Receptors, Adrenergic, beta physiology, Renin biosynthesis, Up-Regulation drug effects, Calcitriol pharmacology, Calcium blood, Hypovolemia blood, Kidney drug effects, Receptors, Adrenergic, beta metabolism, Renin blood, Up-Regulation physiology
- Abstract
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.
- Published
- 2013
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