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Biomedical subjects

J B Puschett

Publications and source records attributed to J B Puschett.

At least 109 records · Page 6Linked to original sources
PubMed1977

Effects of volume expansion and parathyroid hormone on total renal blood flow and its intracortical distribution.

Clearance and renal blood flow studies were performed during hydropenia, 2.5 and 10 percent steady-state saline expansion, and acute administration of parathyroid hormone (PTH) in chronically thyroparathyroidectomized (TPTX) dogs and during hydropenia and 10 percent expansion in intact dogs. Renal cortical blood flow distribution was measured with radioactive microspheres In TPTX dogs, 2.5 percent expansion increased sodium excretion but did not alter total or intracortical blood flow. With 10 percent expansion, sodium excretion and juxtamedullary (zone 4) blood flow increased in both TPTX and intact dogs. There was no correlation between the changes in sodium excretion and zone 4 fractional blood flow in either group. Although the acute administration of PTH to TPTX dogs did not alter total or intracortical blood flow, control period hemodynamic data revealed an inner shift of flow in TPTX as compated to intact dogs.These results indicate that (1) massive (10 percent), but not mild (2.5 percent), volume expansion produces an inner shift of cortical blood flow; (2) this shift does not correlate with sodium excretion, nor is it influenced by thyroparathyroidectomy: and (3) PTH does not acutely alter renal blood flow distribution, but its chronic absence is associated with a shift of flow to the inner cortex.

Animals↗
PubMed1976

Acute effects of parathyroid hormone on proximal bicarbonate transport in the dog.

Re-collection micropuncture and simultaneous clearance studies were performed in thyroparathyroidectomized (TPTX) dogs to evaluate the effects of the acute administration of parathyroid hormone (PTH) on bicarbonate reabsorption. The i.v. administration of PTH from 74 to 94 U/hr reduced proximal fractional reabsorption (FRHCO3) from 0.28 +/- 0.03 to 0.14 +/- 0.03 (P less than 0.005) and absolute bicarbonate reabsorption (THCO3) from 556 +/- 126 to 255 +/- 73 pmoles/min (P less than 0.05), whereas there were no changes in PCO2 (37.0 +/- 1.4 leads to 37.2 +/- 1.4 mm Hg, P greater than 0.90), plasma bicarbonate (PHCO3) (18.5 +/- 0.4 leads to 18.3 +/- 0.4, P less than 0.60), single nephron glomerular filtration rate (102.2 +/- 15;9 leads to 90.1 +/- 10.3 nl/min, P greater than 0.40), serum ultrafilterable phosphate concentration (SUFp) (1.71 +/- 0.13 leads to 1.83 +/- 0.12 mmoles/liter, P greater than 0.25), or serum ultrafilterable calcium (SUFCa) (1.85 +/- 0.05 leads to 1.88 +/- 0.05 mEq/liter, P greater than 0.60). PTH also reduced proximal fractional fluid (and sodium) reabsorption (0.40 +/- 0.04 leads to 0.28 +/- 0.08, P less than 0.05) while TFHCO3 did not change (20.5 +/- 0.4 leads to 20.8 +/- 0.4 mmoles/liter) indicating a rejection of bicarbonate proportional to the inhibition in tubular fluid transport. The invariable reduction in proximal bicarbonate reabsorption did not uniformly result in an increased urinary bicarbonate concentration.

Animals↗
PubMed1975

Parathyroid hormone and 25-hydroxy vitamin D3: synergistic and antagonistic effects on renal phosphate transport.

The effect on phosphate excretion of graded doses of parathyroid hormone (PTH) and the biologically active vitamin D3 metabolite, 25-hydroxycholecalciferol (25-HCC), administered singly and in combination, were studied in the nonexpanded, vitamin D-depleted thyroparathyroidectomized rat. Infusion of 1 unit of 25-HCC per hour for 6 hours induced an antiphosphaturia only when administered with 0.2 units of PTH per hour, while neither agent alone changed phosphate excretion. A dose of 2.0 units of PTH per hour did not cause phosphaturia unless given with 1 unit of 25-HCC per hour. In pharmacologic dosage (5 units per hour), PTH produced phosphaturia in the absence of the metabolite.

Animals↗
PubMed1975

Long-term therapy of viramin D-resistant richets with 25-hydroxycholecalciferol.

The long-term effects of the vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), were evaluated in 2 children with hypophosphatemic vitamin D-resistant rickets. Serial total balance studies demonstrated an apparent lack of correlation between the effects of the vitamin on intestinal absorption of calcium and phosphorus and both the onset of healing in 1 of the 2 patients treated with 5,000 to 7,500 u of the metabolite and the absence of demonstrable radiologic improvement in another patient in whom the final dosage was 20,000 u. per day. At first, the metabolite induced a positive calcium balance in both patients resulting largely from a reduction in intestinal calcium excretion. Despite a continued positive calcium balance, 1 of the 2 patients did not demonstrate further healing, while in the other patient healing was noted even when total calcium balance was negative. Serum phosphate levels did not return to normal in either patient, nor was phosphate excretion altered by 25-HCC. Serum alkaline phosphatase remained elevated in both. Serum immunoassayable parathyroid hormone levels were consistently normal to high-normal in the 2 patients throughout more than 24 months of observation. No instances of hypercalcemia and only occasional hypercalciuric episodes were noted.

Alkaline Phosphatase↗
PubMed1974

Study of the renal tubular interactions of thyrocalcitonin, cyclic adenosine 3',5'-monophosphate, 25-hydroxycholecalciferol, and calcium ion.

Acute clearance studies were performed in thyroparathyroidectomized animals to determine the actions and interactions of thyrocalcitonin (TCT), cyclic adenosine 3'5'-monophosphate (cAMP), 25-hydroxycholecalciferol (25HCC), and calcium ion on the reabsorption of phosphate, calcium, sodium, and potassium by the kidney. The infusion of 25HCC in a dosage of 60 U/h to moderately saline-expanded animals (2.5% body weight) induced a fall in the excretion of all of the ions under study after 90-120 min similar to that observed in previous experiments from this laboratory. Mean decrements in fractional excretion were: phosphate, 42.0% (P < 0.005); calcium, 25.0% (P < 0.005); sodium, 23.4% (P < 0.001); and potassium, 14.7% (P < 0.005). The superimposition of either porcine or salmon TCT (1-100 MRC U/h for 2 h) resulted in no further alterations in electrolyte excretion. However, the infusion of TCT during steady-state saline expansion, before the administration of 25HCC, obviated the renal transport effects of the vitamin D metabolite. Both in the latter studies, as well as those in which similar doses of TCT were given to hydropenic animals, the hormone itself failed to induce any consistent alteration in electrolyte excretion. Cyclic AMP (50 mg/h) caused an increase in the excretion of phosphate, sodium, and potassium and no change in calcium excretion. Like TCT, the nucleotide blocked the action of 25HCC on the kidney. Raising the mean level of serum ultrafilterable calcium to 3.02+/-0.25 mEq/liter from 1.62+/-0.17 mEq/liter likewise prevented enhanced ionic reabsorption due to 25HCC.

Absorption↗
PubMed1972

Evidence for a direct action of cholecalciferol and 25-hydroxycholecalciferol on the renal transport of phosphate, sodium, and calcium.

Acute clearance studies were performed in stable thyroparathyroidectomized dogs to evaluate the possibility of a direct renal action of vitamin D and its biologically active 25-hydroxylated metabolite. Alterations in renal hemodynamics and serum calcium concentration were minimized and attempts at vitamin D depletion were not undertaken. Steady-state volume expansion of modest degree was employed as the control experimental situation so that an effect of the vitamin to enhance phosphate reabsorption would not go undetected because of an already maximal phosphate reabsorptive rate secondary to parathyroidectomy. Under these experimental circumstances, 10,000 U of cholecalciferol and 25-120 U of 25-hydroxycholecalciferol (25-HCC) produced significant depressions in the percentage of filtered phosphate excreted (mean declines of 39 and 47%, respectively), which were not attributable to alterations in renal hemodynamics or to changes in the levels of serum calcium or phosphate. There was an accompanying decline in sodium and calcium excretion; mean percentage excretion rates for sodium fell by 38% with vitamin D and 26% with 25HCC, and for calcium this measurement declined by 46 and 23%, respectively. Furthermore, parathyroid hormone and 25HCC produced antagonistic effects on phosphate excretion. These observations provide the first conclusive evidence for a direct (proximal) tubular action of vitamin D to promote phosphate (as well as sodium and calcium) transport.

Animals↗
PubMed1972

Lithium-induced nephrogenic diabetes insipidus: in vivo and in vitro studies.

The physiological basis for the polyuria and polydipsia occurring in some manic-depressive patients treated with lithium salts was studied in vivo and in vitro. Three lithium-treated polyuric patients, in whom other causes of a concentrating defect were excluded, had abnormal urinary concentrating abilities after a standard water depreviation test. Two of these patients failed to respond to exogenous vasopressin (ADH) and one had a subnormal response. The abilities of these patients to excrete solute-free water (C(H2O)) was comparable to normal subjects during steady-state water diuresis, suggesting no gross abnormalities in sodium transport. However, each of these patients demonstrated abnormally low capacities to reabsorb solute-free water (T(C) (H2O)) under hydropenic conditions after administration of hypertonic saline and vasopressin. These in vivo findings demonstrate at least a nephrogenic basis for the diabetes insipidus syndrome manifested by these three patients. The defect in water transport was further characterized in toad urinary bladders in vitro. Short-circuit current (I) and water flow (W) were studied under basal, ADH-stimulated, and cyclic adenosine 3',5'-monophosphate (c-AMP)-stimulated conditions. Increasing mucosal [Li(+)] progressively inhibited basal I, and both I and W induced by ADH. Significant inhibition of basal and ADH-induced I was observed at mucosal [Li(+)] < 1.1 mEq/liter, and of ADH-induced W at mucosal [Li(+)] = 11 mEq/liter. On the other hand, at these lithium concentrations, neither c-AMP-stimulated W nor I was inhibited. Increasing serosal [Li(+)] produced significant inhibition of basal I only at [Li(+)] at least 50-fold greater than at the mucosal (urinary) surface. These in vitro studies confirm that mucosal lithium inhibits the action of ADH, but not c-AMP. Hence, lithium appears to be a significant inhibitor of ADH-stimulated water flow, probably acts from the urinary surface, and appears to exert its effect at a site biochemically proximal to c-AMP action.

Adult↗
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↗
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

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↗