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

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 chan ges in calcium, magnesium, PTH and calcitonin concentrations. Femoral arter ies and veins of anesthetized male rabbits were cannulated to monitor vital signs, blood sampling and infusion of the agents being studied. Infusion o f 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 m g/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 +/- 27.1 pg/ml. In a separate experiment, calcium gluconate solution was simultaneously infused to keep calcium concentrations steady, thereby p roving a calcium 'clamp'. In normal calcium concentration, ET-1 infusion gr adually decreased PTH concentrations from 71.4 +/- 86 to 38.0 +/- 6.2 pg/ml . We further infused sodium citrate solution to decrease the calcium concen tration (20 mg/dl less) and calcium gluconate solution was infused to keep calcium concentrations steadily less than normal. PTH concentrations were i nitially 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 signiilcantly throughout the entire study and calcitonin concentrations were not signific antly changed during the calcium clamp studies. Serum phosphate and 1,25-(O H)(2) vitamin D-3 concentrations were also measured, but they also did not change significantly. In conclusion, ET-1 exhibited an in vivo acute hypoca lcemic action, independent of calcitonin. It also directly decreased PTH se cretion if serum calcium concentrations were kept steady. The above finding s are consistent with the results of our previous in vitro experiment.