Chronic calcitonin administration and renal calcium transport in the rat

1. While calcitonin (CT) has now been clearly demonstrated to be a renal Ca2+-conserving hormone and may share similar transport mechanisms with parathyroid hormone (PTH), the effect of prolonged CT exposure on renal Ca2+ transport has not been evaluated. 2. Consequently, a submaximal and maximal Ca2+-conserving concentration of human CT was infused into groups of anaesthetized acutely thyroparathyroidectomized rats that had been treated with twice daily subcutaneous human (h) CT at a low or high dose or vehicle for 12 days. 3. The maximal hCT infusion (10 microg bolus and per hour) produced a marked inhibitory effect on renal Ca2+ excretion in vehicle-treated rats, with the fractional excretion rate of Ca2+ being reduced from 4.49+/-0.31 to 139+/-0.23% (P<0.001). However, in rats pretreated with high concentrations of hormone (0.25 microg hCT) twice daily for 12 days, marked Ca2+ conservation was measured (fractional excretion 1.09+/-0.18%), which was not altered by the additional intravenous administration of maximal hCT. 4. Renal Mg2+ transport was similarly altered by hCT administration, without any evidence that prolonged CT inhibited renal Mg2+ transport. The increase in glomerular filtration rate caused by hCT also appeared to persist with repeated hormone administration. The fractional excretion of Na+ and PO4 was significantly increased by high- but not low-dose hCT treatment and was not altered by the addition of a maximal hormone dose at day 12. 5. The present study failed to demonstrate any down-regulation of the response to prolonged hCT administration when renal Ca2+ and Mg2+ transport was measured. If renal escape does occur with CT, as has been suggested but not proven with PTH, other mechanisms, such as hormone production or release, may be responsible.