In vivo effect of endothelin-1 on plasma calcium and parathyroid hormone concentrations

Abstract

We have previously reported an in vitro inhibitory effect of endothelin-1 (ET-1) on parathyroid hormone (PTH) secretion. In the present experiment, ET-1 was infused into rabbits to study the in vivo effect of ET-1 on the changes in calcium, magnesium, PTH and calcitonin concentrations. Femoral arteries and veins of anesthetized male rabbits were cannulated to monitor vital signs, blood sampling and infusion of the agents being studied. Infusion of ET-1 (1, 5, 10 and 20 ng/kg per min) induced a dose-dependent decline in plasma ionized calcium concentrations from 6·68 0·26 to 5·50 0·46 mg/dl (P<0·05) and a decrease in calcitonin concentrations from 48·6 6·5 to 32·5 4·7 pg/ml. PTH concentrations increased from 58·3 10·2 to 159·4 22·1 pg/ml. In a separate experiment, calcium gluconate solution was simultaneously infused to keep calcium concentrations steady, thereby proving a calcium 'clamp'. In normal calcium concentration, ET-1 infusion gradually decreased PTH concentrations from 71·4 8·6 to 38·0 6·2 pg/ml. We further infused sodium citrate solution to decrease the calcium concentration (2·0 mg/dl less) and calcium gluconate solution was infused to keep calcium concentrations steadily less than normal. PTH concentrations were initially stimulated by the induction of hypocalcemia (68·1 11·2 to 135·6 8·5 pg/ml), but decreased by ET-1 infusion (135·6 8·5 to 85·1 15·2 pg/ml). Plasma magnesium concentrations did not change significantly throughout the entire study and calcitonin concentrations were not significantly changed during the calcium clamp studies. Serum phosphate and 1,25-(OH) 2 vitamin D 3 concentrations were also measured, but they also did not change significantly. In conclusion, ET-1 exhibited an in vivo acute hypocalcemic action, independent of calcitonin. It also directly decreased PTH secretion if serum calcium concentrations were kept steady. The above findings are consistent with the results of our previous in vitro experiment.

Parathyroid hormone is inversely related to endothelin‐1 in patients on haemodialysis

“…With regard to this central issue, the results of the present study seem to be consistent with data by Chang et al. 12–14 Indeed, the multiple regression analysis showed an inverse and independent relationship between the circulating levels of PTH and ET‐1 in a group of haemodialysed patients. Therefore, as PTH was the dependent variable, we hypothesize that ET‐1 could represent a factor modulating PTH concentration.…”

“…Successively, these findings were confirmed in vivo in not uraemic rabbits, 14 and in vitro in human parathyroid cells obtained from 11 uraemic patients having severe hyperparathyroidism 13 …”

“…Previous studies 12–14 have shown that ET‐1 could play a role as a regulating factor of PTH secretion; however, none of these studies was designed to verify the existence of such a relationship in patients with CKD.…”

“…Previous experimental studies on parathyroid cell lines or on animals, have demonstrated that ET‐1 can influence PTH secretion 12–14 …”

“…Chang et al. demonstrated that ET‐1 can inhibit PTH secretion both in bovine 12 and human parathyroid cells in vitro , 13 and in the rabbit in vivo 14 …”