Parathyroid, renal, and skeletal responses to induced hypocalcemia in the dog

This study was designed to determine 1) whether the plasma immunoreactive parathyroid hormone (IPTH) response to acutely attained, constant (8 h) hypocalcemia is biphasic, and 2) if so, how kidney and bone respond to these changing plasma IPTH levels. We initiated constant hypocalcemia (decrement of Ca, 1.7 mg/dl) in six conscious dogs using the "calcium clamp" technique. Plasma IPTH concentrations increased maximally (fivefold) within 15 min and then decreased gradually over 1 h to a constant, but still elevated level (3.2-fold increase). Urinary excretion of phosphate and hydroxyproline increased more slowly, reaching plateaus at 1.75 h (76% increase) and 5.5 h (70% increase), respectively. The EGTA infusion rate required to maintain constant hypocalcemia was virtually constant (85 +/- 9 mumol.kg-1.h-1) after 20 min and corresponded to skeletal release of about 80 mg Ca.kg-1.day-1. The contribution of the kidney in conserving filtered calcium was relatively minor (2.0 +/- 0.5 mumol.kg-1.h-1). These data demonstrate that the parathyroid response to acute, constant hypocalcemia is biphasic and is temporally divergent from the uniphasic phosphaturic and hydroxyprolinuric responses. The ensuing increased skeletal release of calcium is very high and is maximal within minutes.