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

Abstract

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 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.