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Nephrology Dialysis Transplantation, Vol 14, Issue 3 604-609, Copyright © 1999 by Oxford University Press


ORIGINAL ARTICLES

Rapid recovery of plasma ionized calcium after acute induction of hypocalcaemia in parathyroidectomized and nephrectomized rats

E Lewin, W Wang and K Olgaard
Nephro-Endocrinological Laboratory, Nephrological Department P2131, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark; Corresponding author

Background. Plasma ionized calcium (Ca2+) is extremely tightly regulated in normal mammals. Even a small decline in Ca2+ is followed by a fast and steep increase of the parathyroid hormone (PTH) secretion and the current understanding of the calcium homeostasis indicates that PTH is the main factor responsible for this tight minute-to-minute regulation of the normal plasma Ca2+ concentration. However, experiments from our laboratory and some clinical experiences points towards the existence of factors, other than PTH, involved in the rapid minute-to-minute calcium homeostasis. Thus, the aim of the present study was to examine whether PTH plays an important role in the rapid upregulation of plasma Ca2+ after induction of hypocalcaemia in the rat. Methods and results. I. Parathyroidectomy (PTX) was performed in seven rats; 60 min later no PTH was detectable in the circulation. Then by a brief infusion of EGTA plasma Ca2+ was reduced from 1.26±0.02 to 0.86±0.02 mmol/l, P<0.001. Despite there being no PTH in the circulation plasma Ca2+ increased significantly to 0.97±0.02 mmol/l already 10 min after discontinuation of the EGTA infusion, P<0.04, and plasma Ca2+ was normalized within another 2 h. II. To evaluate a possible role of renal Ca2+ handling in the rapid upregulation of plasma Ca2+ a group of eight rats had acute PTX and bilateral nephrectomy (NX) performed; 60 min later plasma Ca2+ was reduced from 1.18±0.01 to 0.86±0.02 mmol/l by an EGTA infusion. Despite there being no PTH and no kidneys present plasma Ca2+ increased significantly already 10 min after discontinuation of EGTA to 0.96±0.02 mmol/l, P<0.02. After another 1.5 h the plasma Ca2+ reached the levels of the PTX/NX control rats. III. In order to exclude a possible action of receptor-bound PTH, which may have lasted for more than 1 h, seven rats were PTX 24 h before the induction of hypocalcaemia. Basal plasma Ca2+ was significantly reduced to 1.07±0.01 mmol/l, P<0.01. Then plasma Ca2+ was further reduced to 0.79±0.03 mmol/l by EGTA. Ten minutes after discontinuing EGTA plasma Ca2+ increased to 0.91±0.02 mmol/l, P<0.03 and 60 min later plasma Ca2+ reached the level of the control PTX rats. Normal rats with intact parathyroid glands had an exactly similar response of plasma Ca2+ to EGTA as that of 24 h PTX rats, but at significantly higher levels of plasma Ca2+ with a fall from 1.28±0.01 to 0.96±0.03 mmol/l and again a significant increase of plasma Ca2+ to 1.13±0.03 (P<0.001) 10 min after discontinuation of EGTA. After another hour basal levels were reached. Conclusions. Despite there being no PTH in the circulation a rapid increase of plasma Ca2+ occurs immediately after a brief induction of hypocalcaemia. The kidneys are not responsible for this phenomenon. The present results suggest the existence of a mechanism other than the effect of PTH, which is responsible for the rapid minute-to-minute regulation of plasma Ca2+ in the rat. Keywords: bilateral nephrectomy; parathyroid hormone; parathyroidectomy; recovery from hypocalcaemia; regulation of plasma Ca2+
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K. Olgaard and E. Lewin
Can Hyperparathyroid Bone Disease Be Arrested or Reversed?
Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 367 - 373.
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