Effect of metabolic acidosis on renal action of parathyroid hormone
Beck, N.; Kim, H.P.; Kim, K.S.
American Journal of Physiology 228(5): 1483-1488
1975
ISSN/ISBN: 0002-9513 PMID: 236671 Document Number: 94231
Sprague-Dawley rats of bodyweight 270 to 290 g were parathyroidectomised and for 6 days were given CaCl, 1 g/100 ml of drinking water. On day of test the rats were in 3 groups given intraperitoneally 1.5 mmoles of NaHCO3 (alkalotic), NaCl (control) or NH4Cl (acidotic) with inulin. Bladder urine was collected simultaneously with intravenous infusion of a solution containing 140 mmoles/litre of NaHCO3, NaCl or NH4Cl with inulin 0.3 mg/ml. The intravenous infusion was started 30 min after the intraperitoneal and lasted for 2.5 h. Arterial blood pH and bicarbonate concentrations and the phosphate excretion rates were measured. In the second experiment, similar to the first, three 15-min urine samples were taken before bovine parathyroid hormone (PTH) was given by vein to each rat; urine was collected every 15 min thereafter. Blood was also sampled. In a third experiment cyclic AMP was infused into the control and acidotic rats at 50 mu g/min. Arterial blood pH and bicarbonate concentration were highest in the alkalotic and least in the acidotic rats; the values for each group were stable during the experiments. The acidotic rats had significantly higher concentration in plasma of ionized Ca than the control. There was no real difference between the groups in plasma phosphate concentration, glomerular filtration rate or filtered load of phosphate. The control and the acidotic rats had similar values for extracellular fluid volume measured by 36Cl space and urinary excretion rates of water and chloride. The changes of tubular reabsorption rate of phosphate and urinary excretion of cyclic AMP by PTH were significantly inhibited in the acidotic animals, but the phosphaturia induced by an infusion of dibutyryl cyclic AMP was not affected by metabolic acidosis. The increase of cyclic AMP concentration by PTH was significantly less in the renal cortical slices obtained from the acidotic rats than in those from the controls. The activation of adenylate cyclase by PTH was also significantly inhibited in the acidic media. The findings suggested that in metabolic acidosis the renal response to PTH is decreased and that the decrease is due to the inhibition of the PTH-dependent cyclic AMP system in the kidney at the level of adenylate cyclase in the renal cortex.