Failure of Selected Endocrine Organ Ablation to Modify the Natriuresis of Blood Volume Expansion in the Dog

Abstract

1. Selected organ-ablation experiments were performed in dogs in an attempt to identify the source of the natriuretic hormone postulated to participate in the natriuresis of blood volume expansion. 2. An isolated dog kidney perfused with blood from the femoral artery of deoxycorticosterone-loaded dogs subjected to acute volume expansion with equilibrated blood served as the bioassay system for the natriuretic factor. Four groups were studied after the following procedures: group I, no ablation; group II, thyroparathyroidectomy; group III, hypophysectomy; group IV, adrenalectomy. 3. In all groups, the administration of equilibrated blood promoted a significant increase in sodium chloride excretion in the isolated kidney. The natriuresis was unrelated to changes in glomerular filtration rate, renal blood flow, renal arterial pressure, plasma protein concentration or packed cell volume. In the absence of volume expansion, sodium chloride excretion in the isolated kidney did not change or decreased. 4. These results argue against the thyroid, parathyroid, adrenal and pituitary glands as the source of natriuretic hormone.

Evidence that the Brain Participates in the Humoral Natriuretic Mechanism of Blood Volume Expansion in the Dog

“…Moreover, because the perfusion dog was preloaded with deoxycorticosterone and received a continuous infusion ofvasopressin, decreases in the circulating levels of these hormones were excluded also as possible factors that influence the natriuretic response. These observations confirm our previous studies (3)(4)(5) and are consistent with the hypothesis that the increased sodium excretion from the isolated kidney is mediated by a humoral factor activated by expansion of the dog's blood volume.…”

“…Studies in our laboratory also support the hypothesis that a humoral mechanism, unrelated to mineralocorticosteroid or vasopressin, participates in the natriuretic response elicited by expansion of the blood volume (3)(4)(5). We have used a cross-circulation technique involving an isolated dog kidney connected to the circulation of an intact dog and have observed that infusing equilibrated blood into the dog promotes a significant increase in sodium excretion in the isolated kidney.…”

“…We are impressed by the fact that of the four organ ablation studies performed in this experimental model (5), only the maneuver of decapitation has abolished the humoral natriuretic mechanism. This observation suggests that the brain is either the source of the factor or that the brain participates in the reflex activation of this factor from some other site.…”

“…Because the natriuresis could not be explained by changes in renal hemodynamics or physical factors, we postulated that expansion ofthe dog's blood volume stimulated release of a natriuretic factor, which promoted an increase in sodium excretion by the isolated kidney. In a previous study (5) we sought to identify the source of this factor by examining the effect of selected organ ablation upon the natriuretic response of the isolated kidney during blood volume expansion and were able to exclude the adrenal glands, the thyroparathyroid glands, and the hypophysis as the source of this factor. The purpose of the present investigation was to evaluate the possibility that the postulated natriuretic factor might derive from some site in the brain other than the hypophysis or that the brain might play a role in activating the humoral natriuretic mechanism.…”

Does plasma immunoreactive ouabain originate from the adrenal gland?

“…However, no evidence has been available to support the presence of ouabain in the anterior pituitary. 13 In contrast, we have recently shown the presence of immunoreactive ouabain in the hypothalamus, 14 suggesting a hypothalamic origin of endogenous ouabain. 15 It is not known, however, whether the hypothalamic ouabain is released into the circulation, and if so, how the pituitary tumor affects the hypothalamic ouabain.…”