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Biomedical subjects

M Goldberg

Publications and source records attributed to M Goldberg.

At least 775 records · Page 43Linked to original sources
PubMed1971

Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog.

To evaluate the effects of parathyroid hormone and cyclic adenosine monophosphate on proximal tubular sodium and phosphate reabsorption, micropuncture studies were performed on dogs that received a highly purified preparation of parathyroid hormone (PTH), dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP), 5'-AMP, and saline. PTH resulted in a 30-40% inhibition of sodium and phosphate reabsorption in the proximal tubule unassociated with a rise in either total kidney or single nephron glomerular filtration rate (GFR). The bulk of the phosphate rejected proximally was excreted in the final urine while sodium excretion rose minimally despite the marked proximal inhibition, consistent with the presence of reabsorptive sites in the distal nephron for sodium but not phosphate. The infusion of dibutyryl cyclic AMP either systemically or directly into the renal artery inhibited proximal sodium and phosphate reabsorption in the absence of changes in either total kidney or single nephron GFR, resembling the effects of PTH quantitatively and qualitatively. In contrast, another adenine nucleotide, 5'-AMP, did not inhibit the reabsorption of either sodium or phosphate. These observations support the thesis that renal effects of PTH are mediated via stimulation of renal cortical adenyl cyclase. The infusion of a moderate saline load, 25 ml/kg, also produced a similar inhibition of proximal tubular fractional sodium and phosphate reabsorption with a marked phosphaturia but only minimal natriuresis. Thus, changes in sodium and phosphate reabsorption occur in parallel in the proximal tubule when sodium reabsorption is inhibited either with volume expansion or with administration of "specific" phosphaturic agents such as PTH or cyclic AMP. These data are consistent with the thesis that phosphate reabsorption is dependent upon proximal tubular sodium reabsorption wherein the phosphaturic effect of PTH might be the result of a primary inhibition of proximal tubular sodium reabsorption mediated by adenyl cyclase stimulation.

Adenine Nucleotides↗
PubMed1971

Role of antidiuretic hormone in the abnormal water diuresis of anterior hypopituitarism in man.

To evaluate the role of antidiuretic hormone (ADH) in the defect in water excretion which is characteristic of glucocorticoid deficiency, the effects of hydrocortisone and ethanol upon urinary dilution during a sustained water load were studied in patients with anterior hypopituitarism. A spectrum of defects in urinary dilution was found in the seven patients with anterior hypopituitarism, and the subjects were separable into two groups. Four patients were unable to excrete a urine hypotonic to plasma (group I) while three diluted the urine (group II). In two of the group II patients, despite maintenance of hydration, urinary osmolality later rose to hypertonicity. Physiological doses of hydrocortisone improved urinary dilution in all patients. Submaximal doses of oral hydrocortisone, when given to the group I patients, converted their response to hydration to one characteristic of the group II patients, i.e., an initial hypotonic urine followed by a secondary rise to hypertonicity. Ethanol, a known inhibitor of ADH secretion, had no effect in the group I patients. When two of these patients were pretreated with sub-maximal doses of hydrocortisone, however, so that they were able to transiently dilute the urine, ethanol prevented the secondary rise in urine osmolality. Similarly, the administration of ethanol to the untreated group II patients, when the urine was hypotonic, improved diluting ability as characterized by a lowering of urinary osmolality and an increased excretion of solute-free water in all three patients. Hydrocortisone did not improve urinary dilution in three patients with complete hypophyseal diabetes insipidus and one with both anterior and posterior insufficiency receiving constant infusions of vasopressin. These data suggest, therefore, that inappropriately elevated levels of ADH play a major role in the defect in water excretion of anterior hypopituitarism. Glucocorticoids appear to be necessary for a normal neurohypophyseal response to inhibitory stimuli.

Diabetes Insipidus↗
PubMed1970

Effects of increased sodium delivery on distal tubular sodium reabsorption with and without volume expansion in man.

The separate effects of volume expansion and of increased delivery of sodium on sodium reabsorption in the diluting segment of the distal nephron were studied in man. In six normal subjects during a sustained water diuresis, sodium delivery to the distal nephron was increased without volume expansion by the administration of acetazolamide. In these subjects, free water clearance rose linearly as a function of urine flow. In five patients with complete, central diabetes insipidus, distal sodium delivery was increased by the infusion of hypertonic saline during a sustained water diuresis. In four of these five patients, changes in free water clearance were also observed during hypertonic saline diuresis in the presence of distal blockade of sodium reabsorption with chlorothiazide. At high rates of distal delivery the following observations were made: (a) free water clearance was lower and fractional sodium excretion higher during saline diuresis compared to acetazolamide diuresis; (b) although free water clearance was moderately reduced by chlorothiazide at low rates of urine flow, there was no difference in free water clearance between saline loading alone and saline plus chlorothiazide at high rates of urine flow; and (c) during saline loading free water clearance rose without evidence of a limit when increased distal delivery was accompanied by spontaneous increases in glomerular filtration rate, but tended toward a limit when glomerular filtration rate remained constant. The data indicate that during acute volume expansion with saline, there is a decrease in the fraction of delivered sodium reabsorbed in the distal nephron when compared to the response of the distal nephron to comparable increases in distal sodium delivery in the absence of volume expansion.

Acetazolamide↗
PubMed1969

Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse.

Since either aspirin or phenacetin might be causative in the nephropathy of analgesic abuse, studies were designed to examine the renal accumulation and distribution of the major metabolic products of these compounds, salicylate and N-acetyl-p-aminophenol (APAP) respectively, in dogs. Nineteen hydropenic animals were studied, of which seven were given phenacetin, nine received acetyl salicylic acid, two were given both aspirin and phenacetin, and one received APAP directly. Two of three hydrated animals were given phenacetin and one was given aspirin. During peak blood levels of salicylate and (or) APAP, the kidneys were rapidly removed, frozen, sliced from cortex to papillary tip, and analyzed for water, urea, APAP, and salicylate. No renal medullary gradient for salicylate was demonstrable during both hydropenic and hydrated states. In contrast, both free and conjugated APAP concentrations rose sharply in the inner medulla during hydropenia, reaching a mean maximal value at the papillary tip exceeding 10 times the cortical concentration (P < 0.001), a distribution similar to that of urea. Salicylate had no effect on the APAP gradient, but hydration markedly reduced both the APAP and urea gradients in the medulla. The data indicate that APAP probably shares the same renal mechanisms of transport and accumulation as urea and acetamide, and that papillary necrosis from excessive phenacetin may be related to high papillary concentration of APAP.

Analgesics↗
PubMed1969

Mechanism of exaggerated natriuresis in hypertensive man: impaired sodium transport in the loop of Henle.

To evaluate the effects of saline loading on distal sodium reabsorption in hypertensive man, studies were performed during both water deprivation and water diuresis in eight hypertensive subjects, and the results were compared to data obtained from similar studies in normal subjects. All hypertensive patients exhibited an enhanced excretion of filtered sodium (C(Na)/C(In)) at any level of distal delivery of sodium compared to normal controls. Free water reabsorption (T(c) (H2O)) during hypertonic saline loading was quantitatively abnormal in the hypertensives at high levels of osmolar clearance (C(Osm)), and also the curve of T(c) (H2O) vs. C(Osm) leveled off above a C(Osm) of 18 ml/min per 1.73 m(2) in the hypertensive group in contrast to the normal controls in whom T(c) (H2O) showed no evidence of achieving an upper limit. Sodium depletion exaggerated the abnormality in T(c) (H2O) in hypertensives, and resulted in a positive free water clearance (C(H2O)) during hydropenia. During hypotonic saline loading in water diuresis, changes in free water clearance per 100 ml of glomerular filtrate (C(H2O)/C(In)) were less at any given increment in urine flow per 100 ml of glomerular filtrate (V/C(In)) in the hypertensives compared to normal controls (P < 0.001). This abnormality in C(H2O)/C(In) in the hypertensives in conjunction with the defect in T(c) (H2O) observed during hydropenia indicates that sodium reabsorption in the loop of Henle was abnormal at any given rate of distal delivery of sodium in hypertension. Furthermore, these abnormalities in T(c) (H2O) and C(H2O) coincided temporally with the development of the exaggerated natriuresis. Although the distal defect in sodium transport, in large part, accounted for the augmented natriuresis in hypertension, evidence was present also for enhanced rejection of sodium in the proximal tubule during saline loading in the hypertensives. Additional studies utilizing acetazolamide which increases distal delivery of sodium without extracellular fluid volume expansion showed only minimal abnormalities in C(H2O) in the hypertensive group, indicating that the defect in sodium transport in the loop of Henle in hypertensives is mainly an abnormal response to extracellular fluid expansion rather than an intrinsic defect in the loop to handle increased tubular loads of sodium. It is possible that the abnormality in sodium reabsorption in the loop of Henle is due to the transmission of the abnormally elevated blood pressure of the hypertensives to the medullary vasa recta during saline loading.

Acetazolamide↗