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Calcitonin and electrolyte homeostasis

University of British Columbia

The effects of calcitonin on plasma and urinary electrolytes were studied in rats and sheep. I. Twice-daily administration of salmon calcitonin (250 mU(50 ng)/ 100g rat, i.p.) to young rats over a period of 10 days resulted in increases in urine volume and the excretion of Na, Ca, P, and Mg. Single injections of graded doses of salmon calcitonin (100-2000 mU(20-400 ng)/100g rat, i.p.) resulted in dose-related increases in urine volume and Na excretion over a six-hour period. Phosphate excretion was also found to increase. However, in contrast to the chronic studies, net decreases in the excretion of Ca and Mg were found. Significant decreases in plasma Ca, inorganic P, and Mg were found one hour after injection of 100 mU(20 ng) salmon caIcitonin/100g rat, i.v. No significant decreases in plasma Na and K were observed. The urinary electrolyte changes that occurred following calcitonin administration also occurred in thyroparathyroidec-tomized rats and rats pretreated,with large doses of DOCA (1 mg/100g rat, i. m.), and were not associated with increases in the excretion of endogenous creatinine. 2. A one-hour infusion of Ca (10 mg Ca/kg) in intact conscious sheep was accompanied by a rapid rise in plasma Ca levels which rapidly returned to normal when the infusion was stopped. Plasma P levels immediately decreased following the start of the Ca infusion. Following thyroidectomy (TX), Ca infusion resulted in a significantly greater increase in plasma Ca (Δ2.31±0.10 mg%) as compared to intact sheep (Δ1.60±0.07 mg%), and the return towards normal levels was delayed. Plasma P levels in the TX sheep rose following the start of the infusion, and at 1/2 hour post infusion were significantly higher (Δ+0.42±0.07 mg%) than plasma P in the intact sheep (Δ -0.66±0.22 mg%). In intact sheep, increases in urine volume and the excretion of Na, Ca, P, and Mg were observed during and following the Ca infusion. The TX sheep showed no increase in urine volume, and despite a larger increase in Ca excretion, the excretion of Na in the TX sheep was significantly less than that found in the intact animals. 3. Volume expansion in intact rats (5 ml 0.9% NaCI/100g rat, i.p.) was followed by significant increases in urine volume and the excretion of Na, K, Ca, P, and Mg, but these changes did not occur in TX rats in the three hours following the saline load. Dextran infusion (6% Gentran 75 in 0.9% NaCl) in intact sheep resulted in a sustained fall in plasma Ca levels. When dextran was infused into TX sheep, plasma Ca fell initially but returned to normal within three hours. In both groups of sheep, the volume expansion resulted in a similar increase in Na excretion. However, an increase in Ca excretion did not accompany the natriuresis in the TX sheep, which was in contrast to the findings in the intact animals. 4. Administration of parathyroid extract to TPTX rats (100 U/100g rat, s.c.) decreased the urinary excretion of Na, Ca, and Mg, and increased the excretion of P. In similar studies using highly-purified PTH (3000 U/mg), the excretion of Ca and Mg also decreased and the excretion of K as well as P was found to increase. However, no significant decrease in Na excretion was found. These studies indicated that exogenous administration of salmon calcitonin alters the excretion of Na, Ca, P, and Mg in the urine, in addition to decreasing the levels of Ca, P, and Mg in the plasma. Infusion of Ca salts in intact sheep resulted in certain changes in both plasma and urinary electrolytes which were not found following thyroidectomy in these animals. Since elevation of plasma Ca levels would increase circulating levels of calcitonin in intact but not TX sheep, endogenous release of calcitonin was implicated in the electrolyte changes that were observed. Calcitonin may also be implicated in the plasma and urinary changes that occur following volume expansion since removal of the caIcitonin-containing "C" cells altered the pattern of certain electrolyte changes that occurred in the intact animals following volume expansion. Studies with various PTH preparations suggested that calcitonin and PTH may be acting in antagonistic ways in the renal handling of Na, Ca, and Mg.

Text

2011-03-28

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http://hdl.handle.net/2429/33005

Physiology

University of British Columbia

Graduate