Nephrology Dialysis Transplantation, Vol 14, Issue 3 604-609, Copyright © 1999 by Oxford University Press
E Lewin, W Wang and K Olgaard
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+
ORIGINAL ARTICLES
Rapid recovery of plasma ionized calcium after acute induction of hypocalcaemia in parathyroidectomized and nephrectomized rats
Nephro-Endocrinological Laboratory, Nephrological Department P2131, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark; Corresponding author
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