An Extrarenal Role for Parathyroid Hormone in the Disposal of Acute Acid Loads in Rats and Dogs

Abstract

A B S T R A C T Acid infusion studies were performed in nephrectomized rats and dogs with either intact parathyroid glands (intact) or after thyroparathyroidectomy (thyroparathyroidectomized [TPTX]) to determine the role of parathyroid hormone (PTH) in extrarenal disposal and buffering of acutely administered acid. 29 intact rats given 5 mM/kg HCI and 6 intact dogs given 7 mM/kg HC1 developed severe metabolic acidosis but all survived. However, each of 12 TPTX rats and 4 TPTX dogs given the same acid loads died. Intact rats and dogs buffered 39 and 50% of administered acid extracellularly, respectively, whereas extracellular buffering of administered acid was 97 and 78% in TPTX rats and dogs, respectively. 17 TPTX rats and 6 TPTX dogs given synthetic PTH 2 h before acid infusion survived. The blood bicarbonate and extracellular buffering in these animals, measured 2 h after acid infusion, was similar to intact animals. Changes in liver, heart, and skeletal muscle pH determined from [14C]5,5-dimethyl-2,4 oxazolidinedione distribution seemed insufficient to account for the increased cell buffering of PTH-replaced animals. Indeed, muscle pH in TPTX dogs given PTH and acid was only 0.06 pH units lower than in control dogs given no acid, suggesting that another tissue, presumably bone, was the target for PTH-mediated increased cell buffering. This conclusion was supported by the observation that PTH did not alter the pH of intact rat diaphragms in vitro. These results indicate that PTH is necessary for the optimal buffering of large, acute acid loads presumably by increasing bone buffering.

Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.

“…A high rate of mortality after acid loading was observed in PTX animals in this and previous (23,24) studies. Wachman and Bernstein (40) have reported in normal humans that chronic ammonium chloride loading was associated with negative calcium balance, together with a rise in urinary hydroxyproline levels, phosphate renal clearance, and excretion rate; also, plasma iPTH levels were elevated in two of four cases during metabolic acidosis (40).…”

“…Also, one PTX and one TPTX rat of group II died during the third hour of HCl infusion, as already mentioned, which suggests that extrarenal factors may also have contributed to the poor endurance to acid loading of PTX animals. A high rate of mortality had previously been observed by others during acute acid loading in nephrectomized TPTX animals (23,24).…”

“…A similar hypothesis has also been expressed by Wills (41). Consistent Metabolic Acidosis and Parathyroid Hormdne 441 with the latter hypothesis, several studies (23,24,42), although not all (43), have shown that PTH is necessary for the optimal body buffering of acute acid loads in nephrectomized rats and dogs, probably by increasing bone buffering. Also, in some experimental models of chronic PTH administration in dogs, an extrarenal alkali input into the extracellular fluid compartment, probably from bone, was shown to contribute to the PTH-induced metabolic alkalosis (6, 7).…”

Rapid Correction of Metabolic Acidosis in Chronic Renal Failure: Effect on Parathyroid Hormone Activity

“…Several studies have shown that PTH is necessary for optimal body buffering of acute acid loads in nephrectomized rats and dogs, probably by increasing the bone supply of buffer to the extracellular fluid [24,25], Elevated circulating PTH activity during acute metabolic acidosis had previously been observed in only one study in humans [26]. On the other hand, chronic ammonium chloride load ing in normal humans was associated with a negative cal cium balance, together with a rise in urinary hydroxyproline levels, phosphate renal clearance and excretion rate; moreover, plasma PTH levels were elevated [27], thus suggesting that the chronic acidosis-induced increase in circulating PTH activity can act on the kidney to increase net acid excretion in healthy humans.…”

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

“…Previous in vitro and in vivo studies (62)(63)(64) showed that even in the absence of PTH, metabolic acidosis increases calcium efflux from bone. Moreover, Fraley and Adler (65) showed that the administration of PTH to parathyroidectomized animals that received an acid load increased survival; therefore, the results of these studies suggest not only that in acute metabolic acidosis calcium release from bone is increased independent of PTH but also that PTH acts to enhance calcium release further from bone and to increase buffering capacity. Consequently, there is good evidence to suggest that acute metabolic acidosis besides increasing PTH secretion increases the bone response to PTH.…”