Renal handling of phosphate during extracellular volume expansion and parathyroid hormone administration

To further examine the interaction between the phosphaturic effects of parathyroid hormone (PTH) and extracellular volume expansion (ECVE), clearance studies were performed in chronically and acutely parathyroidectomized (PTX) rats in three sets of experiments. In the first series, two groups of chronically PTX animals (groups 1 and 2) received a PTH infusion (2 U/h). In group 1 ECVE was superimposed on the PTH infusion, while the animals in group 2 received the hormone infusion alone. In the second series the following groups of chronically PTX rats were examined: volume expanded rats (groups 3 and 4) and control normovolemic rats (group 5). A PTH bolus (5 units) was added to group 3 while group 4 underwent volume expansion alone. The third series of experiments compared the response of acutely and chronically PTX rats given a submaximal dose of PTH (1 U/h) with additional ECVE (group 6) or undergoing submaximal ECVE with additional PTH (group 7). In the first set of experiments, the PTH-ECVE rats had a higher inulin clearance (CIn) and phosphate clearance (Cp) than the animals receiving the PTH alone. The maximal fractional excretion of phosphate (Cp/CIn) was similar in both groups. In the second set, GFR was similar in the normovolemic and the volume expanded animals. The two volume expanded groups had a higher Cp/CIn than the control normovolemic animals. The maximal Cp/CIn was 0.234 +/- 0.031 in the ECVE-PTH and 0.235 +/- 0.056 in the ECVE animals (p = NS). No significant difference could be detected during the whole experiment in any variable between the volume-expanded PTH-injected (ECVE-PTH) and ECVE only rats. Acutely and chronically PTX rats responded with a similar degree of phosphaturia after ECVE superimposed on PTH infusion or after PTH superimposed on ECVE. Acutely PTX rats, however, exhibited a significantly delayed response to exogenous PTH as compared to chronically PTX animals. There was no difference in the response to ECVE between the acute and chronically PTX rats. When chronically PTX rats were exposed to submaximal ECVE, the final Cp/CIn was less than after ECVE-PTH, PTH-ECVE or PTH. These findings show that in chronically PTX rats the phosphaturic response to PTX and ECVE is not additive under conditions of maximal stimulation by PTH or ECVE. Examination of acutely PTX animals and use of a different protocol of ECVE disclose a broader spectrum of phosphaturic responses.(ABSTRACT TRUNCATED AT 400 WORDS)