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M A Knepper

Publications and source records attributed to M A Knepper.

205 records · Page 12Linked to original sources
PubMed1981

Mineralocorticoid effects on Na-K-ATPase in individual nephron segments.

A fluorometric micromethod for the assay of Na-K-ATPase was used to determine Na-K-ATPase activity in 11 segments of the rabbit nephron. The Na-K-ATPase activity was found to be highest (greater than 100 pmol.mm1-.min-1) in proximal convoluted tubules (S1), medullary thick ascending limbs, distal convoluted tubules, and connecting tubules. There was a good correlation (r = 0.94) between Na-K-ATPase activity in different segments and net Na transport previously measured by in vitro tubule perfusion. Treatment of rabbits with deoxycorticosterone (DOCA) for 8-11 days produced increases in Na-K-ATPase activity of 100 and 500% in connecting tubules and cortical collecting ducts, respectively, without significant change in other segments. Maintenance on a low sodium diet for 12-18 days was associated with a 200% increase in Na-K-ATPase activity in cortical collecting ducts only. We conclude that the Na-K-ATPase activity is stimulated by mineralocorticoids in the cortical collecting duct in association with the previously observed changes in sodium transport.

Aldosterone↗
PubMed1981

Increased fluid absorption and cell volume in isolated rabbit proximal straight tubules after in vivo DOCA administration.

To investigate whether mineralocorticoids affect the intrinsic capacity of the proximal tubule to absorb sodium and fluid, rabbits were chronically treated a number of ways to systematically vary plasma concentrations of mineralocorticoid hormones. The rate of fluid absorption and tubule dimensions were measured in superficial S2 segments from these rabbits. Chronic administration of deoxycorticosterone acetate (DOCA) was associated with a 67% increase in fluid absorption and a 29% increase in cell volume per unit tubule length. However, neither adrenalectomy nor low sodium diet significantly affected either fluid absorption or cell volume. Furthermore, marked dietary sodium restriction prevented the response to DOCA. We conclude that the DOCA-induced increases in fluid absorption and cell volume do not result from a direct stimulation of the proximal tubular cells by the steroid but more likely are responses to systemic effects of DOCA administration that are dependent on the level of sodium intake. Thus, we find no evidence for a direct mineralocorticoid stimulation of sodium and fluid transport by the S2 portion of the proximal tubule.

Adrenalectomy↗
PubMed1977

Quantitative analysis of renal medullary anatomy in rats and rabbits.

The mean renal tubular diameters, number of tubules per unit of cross-sectional area, and fraction of the total volume occupied by each medullary structure were determined at various levels of the renal medulla of the rat and rabbit. Statistical estimates of anatomic variables were made using spatial sampling techniques on histologic sections. Osmotic diuresis and renal venous occlusion were used to allow fixation of renal tubules and blood vessels in an open state. The distribution of volume fractions of medullary structures are similar in rats and rabbits. Diameters of outer medullary tubular segments and inner medullary thin limbs of Henle are also similar in rats and rabbits. Marked differences between rats and rabbits, however, are seen in the size and number of collecting ducts in the inner medulla. Rabbit inner medullary collecting ducts increase in diameter and decrease in number in the papillary direction relatively closer to the cortex than do those of the rat. Luminal diameters of papillary collecting ducts are more than twice as great in the rabbit as in the rat. An additional finding was that short loops of Henle in the rabbit have their bends relatively closer to the cortex than those of the rat. The quantitative anatomic data derived in this study, when combined through mathematical modeling with knowledge of transport properties of renal tubular membranes, should lead to a clearer understanding of renal function.

Animals↗
PubMed1975

Effects of dietary protein restriction and glucocorticoid administration on urea excretion in rats.

Rats were sampled for clearance studies under anesthesia after 0, 2, 4, 7 and 14 days of dietary protein restriction. Mean fractional urea excretion decreased between day 2 and day 7 of protein restriction after a two-day lag in response. Seven-day administration of dexamethasone in protein-restricted rats caused a significant increase in mean fractional urea excretion. Adrenalectomized rats fed a normal diet had fractional urea excretion values resembling those in protein-restricted rats. Chronic administration of dexamethasone in adrenalectomized rats caused a consistent increase in fractional urea excretion. Fractional urea excretion values were no lower in protein-restricted adrenalectomized rats fed a normal diet. The mean plasma corticosterone concentration (measured 6 to 8 PM) was decreased in rats fed a low protein diet relative to rats fed a high protein diet. The results suggest that glucocorticoids may play a role in the tubular regulation of urea excretion either by a direct effect on the renal tubule or through some intermediate factor. A mediating role of glomerular filtration rate in glucocorticoid-induced changes of fractional urea excretion could not be ruled out, however.

Adrenalectomy↗
PubMedDate not supplied

Disordered water channel expression and distribution in acquired nephrogenic diabetes insipidus.

A series of recent studies have demonstrated that expression of aquaporin-2 (AQP2), the vasopressin-regulated water channel of the kidney collecting duct, is greatly reduced in acquired forms of nephrogenic diabetes insipidus (NDI). In some forms of NDI, there is also impaired delivery of these channels to the apical plasma membrane, where they permit water reabsorption from the urine. The combination of these factors is likely to underlie the urinary concentrating defect that defines these conditions. Direct infusion of vasopressin causes an increase in AQP2 expression, probably via a rise in cytosolic adenosine 3:5-cyclic phosphate, which also acts as the second messenger, triggering the delivery of AQP2 to the plasma membrane. However, it is clear from the studies described that there are also vasopressin-independent pathways that regulate the expression of AQP2, some of which appear to reflect intranephric changes, whereas others involve systemic signals. These studies also show that recovery of AQP2 expression, even after correction of the underlying condition, can be slow, consistent with the clinical observation that recovery of urinary-concentrating ability often takes weeks or months. An understanding of the cellular signals and mechanisms responsible for the decrease in AQP2 expression may make it possible to develop treatments for this common clinical problem.

Animals↗