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T H Steele

Publications and source records attributed to T H Steele.

At least 55 records · Page 3Linked to original sources
PubMed1977

Diuretic-induced uricosuria: interaction with pyrazinoate transport in man.

We investigated the acute effect of an orally administered uricosuric natriuretic agent (SKF-62698) on renal urate transport in paired clearance studies in seven normal men. The participants received SKF-62698 on two separate occasions. Prior to the second study, each received pyrazinamide (PZA) in order to inhibit the tubular secretion of urate. Within 3 hours, SKF-62698 significantly decreased the plasma urate and trebled the rate of urate excretion in the studies without PZA. In contrast, after PZA pretreatment. SKF-62698 did not diminish the plasma urate appreciably and elicited only 60% of the previous increase in urate excretion. Sodium excretion quadrupled after SKF-62698, irrespective of the presence of PZA. Plasma concentrations of pyrazinoate, the renally active metabolite of PZA, were at levels previously shown in the chimpanzee to primarily inhibit the tubular secretion of urate. Therefore, intact tubular secretion of urate probably was necessary in order for SKF-62698 to elicit its maximum uricosuric response. SKF-62698 appeared to inhibit the tubular secretion of pyrazinoate, but the observed changes in urate transport could not be explained on that basis.

Adult↗
PubMed1976

Renal urate transport during variations in urate synthesis in the rat.

In order to determine the effect of intrarenal synthesis of urate upon the urinary urate excretion in the rat, we effected large changes in urate synthesis by increasing it with allopurinol. Hypoxanthine infusion increased plasma urate rapidly and also increased the urinary urate excretion and its renal clearance. However, when the plasma urate was maintained constant, hypoxanthine had no effect upon renal urate transport. Conversely, allpurinol infusion rapidly diminished the plasma urate, urinary urate excretion and its renal clearance. Again, the maintenance of a constant plasma urate concentration prevented any change in urate transport during allopurinol. The urinary degradative purine metabolic pattern was altered predictably by hypoxanthine and allopurinol. Assuming than any putative intrarenal component of urate synthesis would be affected predictably and consistently by hypoxanthine and allopurinol, these results suggest that changes in intrarenal urate synthesis are not an important determinant of urate excretion in the rat.

Allantoin↗
PubMed1976

Renal transport of urate during diuretic-induced hypouricemia.

The effect of two weeks administration of a uricosuric diuretic (SKF-62698) on renal urate handling has been examined in 11 normal men. Plasma urate concentrations had declined by more than 60 per cent after two weeks. Urate excretion per unit of glomerular filtration rate and urate clearance (Curate) per unit of glomerular filtration rate were increased after the administration of SKF-62698. The importance of intact tubular secretion of urate in producing these changes was assessed by administering pyrazinamide, an agent that curtails urate secretion, to each participant. The decrements in urate excretion and clearance produced by pyrazinamide both increased significantly, whereas the residual urate excretion rates and clearances not suppressible by pyrazinamide were only minimally altered by SKF-62698 treatment. These results suggest that the excretion of secreted urate was enhanced by prolonged administration of SKF-62698, probably secondary to the inhibition of postsecretory urate reabsorption. In addition, because the nonsuppressible urate excretion did not decline despite a 63 per cent reduction in the plasma urate, it is likely that the reabsorption of filtered urate also was impaired by SKF-62698.

Adult↗
PubMed1976

Variation of urate excretion with urine flow in normal man.

In normal persons, a decrease in urine flow following the injection of small amounts of vasopressin was accompanied by a significant decrease in the clearance and excretion of urate. When vasopressin and a small natriuretic dose of mannitol were administered together, urine flow and urate excretion again decreased. The recovery of urine flow to control values was accompanied by a similar recovery of urate excretion. Because a natriuretic dose of mannitol did not reverse the antiuricosuric effect of the flow decline, it is postulated that the flow effect probably reflects changes in a component of urate efflux distal to the loop of Henle.

Adult↗
PubMed1976

Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat.

Inorganic phosphate (Pi) reabsorption was studied during Pi infusion, after acute or chronic thyroparathyroidectomy (TPTX), in rats stabilized on a high-phosphorus (1% P) or a low-phosphorus (0.02% P) diet. After acute TPTX, there were no consistent differences in Pi reabsorption between the high- and low-phosphorus dietary groups. After chronic TPTX, the rats stabilized on the low-phosphorus diet exhibited nearly complete Pi reabsorption at every plasma Pi level, while the animals receiving the high-phosphorus diet manifested a marked phosphaturic response to Pi infusion. In addition, Pi reabsorption was significantly increased in the chronic TPTX low-phosphorus rats which achieved the highest filtered Pi loads, while their urine remained essentially phosphate-free. Dietary phosphorus-dependent alterations in Pi reabsorption may play a significant role in establishing the rate of Pi excretion per nephron under certain circumstances and should be considered in the interpretation of studies investigating renal Pi handling. The ability of phosphorus-depleted animals to maintain a phosphate-free urine during Pi loading would favor the rapid repletion of body phosphorus stores.

Absorption↗
PubMed1976

Renal resistance to parathyroid hormone during phosphorus deprivation.

Because previous studies have demonstrated that renal inorganic phosphate reabsorption is enhanced in rats after dietary phosphorus deprivation, we studied the effects of parathyroid hormone (PTH) upon inorganic phosphate reabsorption in acutely thyroparathyroidectomized rats stabilized on a low phosphorus diet to determine if the phosphaturic response to PTH is impaired during phosphorous depletion. Acutely thyroparathyroidectomized phosphorus-deprived rats responded only minimally to PTH, whereas similarly prepared animals stabilized on a high phosphorus diet exhibited a large phosphaturic response. Base-line urinary cyclic AMP values and PTH-induced increases in cyclic AMP excretion were similar in both groups. In other experiments, dibutyryl cyclic AMP elicited a greatly diminished phosphaturic response in phosphorus-deprived rats, as compared to their high phosphorus counterparts. These results indicate that the renal phosphaturic responses to PTH and cyclic AMP are impaired during dietary phosphorus deprivation. The impaired phosphaturia would contribute to phosphorus conservation and to the replenishment of inorganic phosphate stores after phosphorus depletion.

Animals↗
PubMed1976

Pharmacological characterization of lithium reabsorption in the rat.

The effects of furosemide, chlorothiazide and acetazolamide upon fractional lithium excretion (FELi) were studied in acutely lithium-loaded rats. Changes in FELi were compared with the fractional excretions of sodium FENa and calcium FECa. Furosemide and acetazolamide, given separately, produced large and substantially equivalent increases in FELi. Responses of FENa and FECa to acetazolamide were much less than to furosemide. Chlorothiazide, alone or in combination with the other agents, produced moderate increases in FENa, modest increases in FECa and essentially no change in FELi. When furosemide was superimposed upon a previously established acetazolamide diuresis, the response in FELi was additive to that from acetazolamide alone. These results suggest that lithium reabsorption occurs at nephron sites primarily affected by acetazolamide and furosemide in the rat and that a significant amount of lithium reabsorption may take place in the loop of Henle. Acetazolamide, in combination with furosemide, appeared to depress renal tissue lithium accumulation.

Absorption↗
PubMed1976

Selective lithium inhibition of hormonal phosphaturic responses.

The acute effects of intraperitoneal lithium on the phosphaturic responses to parathyroid hormone (PTH) and pharmacologic doses of vasopressin were studied in rats. Lithium significantly inhibited the phosphaturic response to PTH at a dosage of 90 mug/kg/hr but did not affect the response to 30 mug/kg/hr. Conversely, lithium eliminated the phosphaturic response to vasopressin at a dosage of 300 mU/kg/hr but did not affect the response to dibutyryl adenosine 3', 5'-monophosphate (db-cAMP), 10 mg/kg/hr. Renal lithium content was increased substantially after the larger dose of PTH and was diminished slightly after db-cAMP and the larger dose of vasopressin. The latter two treatments also inhibited renal lithium reabsorption whereas the smaller dose of vasopressin and both dosages of PTH did not. These results indicate that lithium interferes with the phosphaturic responses to certain dosages of pth and vasopressin and suggest that renal lithium reabsorption and tissue lithium uptake may in part determine the extent of this cation-hormonal interaction. In addition, a competitive type of interaction between lithium and vasopressin is postulated.

Animals↗
PubMed1975

Renal phosphate reabsorption in the rat: effect of inhibitors.

The maximum rate of inorganic phosphorus (P1) reabsorption (Tmp1) was measured during phosphate infusion in chronically parathyroidectomized rats. In either initially hydropenic rats or others which underwent moderate preliminary saline loading, Tmp1 tended to rise during early phosphate infusion and then decline, so that steady-state Tmp1 values were similar to the P1 reabsorption rates at the animals' own evelated endogenous plasma P1 concentrations. These results indicate that the "self-depression" of Tmp1 during phosphate infusion is not dependent upon the progressive stimulation of endogenous parathyroid hormone secretion. Parathyroid hormone and dibutyryl cyclic adenosine monophosphate (AMP) decreased Tmp1 substantially, whereas acetazolamide inhibited P1 reabsorption at lower filtered P1 loads but did not diminish Tmp1.

Acetazolamide↗
PubMed1975

Phosphatemic action of 1,25-dihydroxyvitamin D3.

The action of a single intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was investigated in thyroparathyroidectomized (TPTX) vitamin D-deficient phosphate-depleted rats. After 14 h, plasma inorganic phosphorus (Pi) was significantly greater in animals receiving 1,25(OH)2D3 than in D-deficient controls, but urinary Pi excretion was very low in both groups and not significantly different in the rats given 1,25(OH)2D3. Clearance studies indicated that the D-deficient controls reabsorbed more than 99% of their filtered Pi. Avid Pi reabsorption continued even after the infusion of sufficient phosphate to raise the plasma and filtered Pi to approximately 3 times normal. Fractional calcium excretion (FECa) exceeded fractional sodium excretion (FENa) by severalfold, but FECa decreased strikingly during phosphate infusion. In animals that manifested a substantial elevation of plasma Pi after 1,25(OH)2D3, FECa was significantly less than in D-deficient controls. Therefore, the increase in plasma Pi following 1,25(OH)2D3 administration occurs independently of any effect on renal Pi reabsorption and may be responsible, at least in part, for the amelioration of hypercalciuria after 1,25(OH)2D3 treatment.

Animals↗
PubMed1975

Renal urate excretion in normal man.

The development of our knowledge of the intrarenal process involved in the control of urate excretion in normal man is summarized. Although there are many gaps in our current knowledge, and different interpretations may be given to the available data, current evidence seems to favor the existence of extensive tubular reabsorption of urate following its glomerular filtration. Subsequently, tubular secretion of urate and the reabsorption of an unknown amount of the secreted urate probably take place. For reasons discussed, it seems most likely that the regulation and control of urate excretion are accomplished through modulations in tubular secretion, post-secretory reabsorption, or both.

Biological Transport, Active↗
PubMed1975

Intrinsic renal disease leading to abnormal urate excretion.

Since approximately two thirds of daily urate production is normally excreted by the kidney, intrinsic renal disease resulting in abnormalities of urate excretion may have a profound effect upon urate homeostasis. Alterations in the pattern of urate excretion encountered in chronic renal failure are reviewed in depth, with a description of adaptive mechanisms for urate excretion which develop in residual nephrons, as exemplified by the remaining normal kidney of transplant donors. In addition, abnormalities in urate excretion in the presence of a normal complement of nephrons are described. Diminished urate excretion per nephron appears to be responsible for hyperuricemia in some patients with gout, while a variety of tubular defects resulting in excessive renal urate excretion have been documented as the basis for some cases of hypouricemia.

Acute Kidney Injury↗
PubMed1975

Diuretics, urate excretion and sodium reabsorption: effect of acetazolamide and urinary alkalinization.

The uricosuric properties of acetazolamide were investigated in order to elucidate the relationship between changes in proximal tubular sodium reabsorption and urate excretion in man. Acetazolamide produced a modest uricosuric response which was not suppressible by pyrazinamide. Alkalinization of the urine with sodium bicarbonate elicited an even smaller increment in the urate clearance. If urinary alkalinization does play a role in the uricosuric response to acetazolamide, it probably decreases urate reabsorption within the distal nephron. The present studies, when taken together with previous work, suggest that alterations in proximal tubular sodium and water reabsorption probably do not play an important role in the normal control of urate excretion or in the pathogenesis of hyperuricemic states. Diuretic-induced hyperuricemia occurring during extracellular fluid volume depletion probably results from either diminished tubular secretion of urate, accelerated postsecretory urate reabsorption, or both.

Acetazolamide↗