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

Background. Plasma ionized calcium (Ca2+) is extremely tightly regulated in normal mammals. Even a small decline in Ca2+ is followed by a Cast and ste ep increase of the parathyroid hormone (PTH) secretion and the current unde rstanding 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 clin ical experiences points towards the existence of factors, other than PTH, i nvolved 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 th e rapid upregulation of plasma Ca2+ after induction of hypocalcaemia in the rat. Methods and results. I. Parathyroidectomy (PTX) was performed in seven rats ; 60min later no PTH was detectable in the circulation. Then by a brief inf usion of EGTA plasma Ca2+ was reduced from 1.26+/-0.02 to 0.86+/-0.02mmol/l , P<0.001. Despite there being no PTH in the circulation plasma Ca2+ increa sed significantly to 0.97 +/-0.02 mmol/l already 10 min after discontinuati on of the EGTA infusion, P<0.04, and plasma Ca2+ was normalized within anot her 2 h. II, To evaluate a possible role of renal Ca2+ handling in the rapid upregul ation of plasma Ca2+ a group of eight rats had acute PTX and bilateral neph rectomy (NX) performed; 60min later plasma Ca2+ was reduced from 1.18+/-0.0 1 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 10min after discontinuation of EGTA to 0.96+/-0.02mmol/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 inducti on of hypocalcaemia. Basal plasma Ca2+ was significantly reduced to 1.07+/- 0.01mmol/l, P<0.01. Then plasma Ca2+ was further reduced to 0.79+/-0.03 mmo l/l by EGTA. Ten minutes after discontinuing EGTA plasma Ca2+ increased to 0.91+/-0.02mmol/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 ex actly 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 Ca2to 1.13+/-0.03 (P<0.001) 10 min after discontinuation of EGTA. After anothe r 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 th e rat.