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Biomedical subjects

B M Brenner

Publications and source records attributed to B M Brenner.

At least 343 records · Page 19Linked to original sources
PubMed1971

Postglomerular vascular protein concentration: evidence for a causal role in governing fluid reabsorption and glomerulotublar balance by the renal proximal tubule.

We tested the relationship between postglomerular microvascular protein concentration and rates of sodium and water transfer by rat proximal tubules. Using recently described microperfusion techniques, efferent arterioles and branch peritubular capillaries of normal hydropenic rats were perfused with colloid-free Ringer's solution, and isoncotic (9.0-10.0 g/100 ml) and hyperoncotic (15 g/100 ml) albumin-Ringer's solutions. Reabsorption in adjacent proximal tubules was studied using free-flow techniques, with initial collections obtained during normal blood perfusion, recollections during experimental microperfusion, and in some tubules, repeat recollections after microperfusion and spontaneous resumption of blood perfusion. Colloid-free perfusion resulted in a uniform inhibition of proximal reabsorption (absolute and fractional). Despite identical techniques, substitution of isoncotic and hyperoncotic perfusates resulted, on average, in unchanged and increased rates of reabsorption, respectively. These findings of direct linear changes in reabsorption in response to changes in postglomerular protein concentrations usually occurred in the absence of significant changes in filtered load, and were nearly always found to be reversible within minutes of cessation of experimental perfusion. Given this evidence of a causal relationship between postglomerular oncotic pressure and proximal reabsorption, we undertook to determine whether this relationship is responsible for the parallel adjustments in proximal reabsorption that follow changes in GFR (glomerulotubular balance). Using a separate group of hydropenic rats, proximal reabsorption was studied, initially during partial aortic constriction (during which renal perfusion pressure, single nephron GFR, absolute proximal reabsorption, and calculated filtration fraction all were reduced below levels prior to constriction), and again while adjacent efferent arteriolar and peritubular capillary protein concentrations, but not GFR, were restored to normal (preconstriction) levels by microperfusion with 9-10 g/100 ml albumin-Ringer's solution. During this dissociation of GFR and postglomerular protein concentration, absolute and fractional proximal reabsorption nearly always increased in parallel with the changes in the latter, thereby demonstrating that glomerulotubular balance is mediated, at least in part, by changes in postglomerular oncotic pressure brought about by changes in filtration fraction.

Animals↗
PubMed1971

On the mechanism of inhibition in fluid reabsorption by the renal proximal tubule of the volume-expanded rat.

We undertook to determine the extent to which the inhibition in absolute proximal fluid reabsorption in response to expansion of extracellular volume with noncolloid-containing solutions is the result of concomitant reductions in postglomerular (efferent arteriolar) protein concentration. Selective elevation of efferent arteriolar oncotic pressure in volume-expanded rats (Ringer's 10% body weight) to levels slightly in excess of normal by microperfusion with 9-10% albumin-Ringer's solution nearly completely reversed the inhibition in absolute and fractional reabsorption in adjacent proximal tubules. In contrast, during similar microperfusion with a 6-7% albumin solution, no increase in proximal reabsorption was measured. We interpret these findings to indicate that the bulk of the inhibition in absolute proximal reabsorption in response to volume expansion with colloid-free solutions is causally mediated by the accompanying parallel decline in postglomerular vascular protein concentration.

Animals↗
PubMed1971

The dynamics of glomerular ultrafiltration in the rat.

Using a unique strain of Wistar rats endowed with glomeruli situated directly on the renal cortical surface, we measured glomerular capillary pressures using servo-nulling micropipette transducer techniques. Pressures in 12 glomerular capillaries from 7 rats averaged 60 cm H(2)O, or approximately 50% of mean systemic arterial values. Wave form characteristics for these glomerular capillaries were found to be remarkably similar to those of the central aorta. From similarly direct estimates of hydrostatic pressures in proximal tubules, and colloid osmotic pressures in systemic and efferent arteriolar plasmas, the net driving force for ultrafiltration was calculated. The average value of 14 cm H(2)O is lower by some two-thirds than the majority of estimates reported previously based on indirect techniques. Single nephron GFR (glomerular filtration rate) was also measured in these rats, thereby permitting calculation of the glomerular capillary ultrafiltration coefficient. The average value of 0.044 nl sec(-1) cm H(2)O(-1) glomerulus(-1) is at least fourfold greater than previous estimates derived from indirect observations.

Animals↗
PubMed1969

An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron.

The evidence from previous micropuncture studies for an inhibitory effect of furosemide on proximal sodium reabsorption in the rat has been conflicting. Intrinsic reabsorptive capacity, estimated in free flow and shrinking drop experiments, has been reported to be depressed, whereas fractional reabsorption usually remains unchanged. We have recently reported that, during conditions of elevated intraluminal hydrostatic pressure, unless care is taken to prevent retrograde flow of tubule fluid from more distal sites, the concentration of inulin in late proximal fluid is often factitiously elevated. Since furosemide raises intraluminal pressures, often markedly, the failure to detect a depression of fractional reabsorption might be the consequence of retrograde contamination during fluid collection. Experiments were designed to compare the effect of furosemide on fractional sodium reabsorption by the proximal tubule when collections were obtained with distal oil blocks of conventional length as well as with unusually long blocks of oil of low and high viscosities. When reflux is prevented, fractional sodium reabsorption is usually depressed by furosemide, whereas when conventional distal blocks are used, the calculated values for fractional reabsorption either remain unchanged or increase. Simultaneous measurements of nephron glomerular filtration rate indicate that the latter is the consequence of retrograde contamination.

Animals↗
PubMed1969

Failure to demonstrate a hormonal inhibitor of proximal sodium reabsorption.

Recently, it has been reported that a humoral inhibitor of proximal sodium reabsorption could be detected in plasma, and dialysates of plasma, of rats and dogs undergoing saline diuresis. We have repeated these studies using similar techniques and protocols. Fractional sodium reabsorption by the proximal tubule (as estimated in free-flow micropuncture studies from tubule fluid-to-plasma inulin ratios) was found not to be lower during infusion of "natriuretic" plasma than during subsequent infusion of "hydropenic" plasma. Similarly, infusion of natriuretic plasma failed to prolong reabsorptive half-time of the shrinking drop beyond that seen during hydropenic plasma infusion. No increase in urine volume or rate of sodium excretion was observed during the period of natriuretic plasma infusion, nor did natriuretic plasma result in an increase in these measures in rats undergoing water diuresis. It also has been reported that dialysates of natriuretic plasma, but not of hydropenic plasma, when placed directly into the tubule lumen, inhibit proximal sodium reabsorption. In double blind studies carried out independently in Bethesda, London, and Cologne, we failed to detect the presence of a dialyzable inhibitor in natriuretic plasma. Finally, in contrast to other recent reports, we were unable to detect inhibitory activity in plasma obtained from dogs during the "escape" phase of chronic deoxycorticosterone acetate administration.

Animals↗
PubMed1969

The relationship between peritubular capillary protein concentration and fluid reabsorption by the renal proximal tubule.

The relationship between peritubular capillary protein concentration and rate of sodium reabsorption by the rat proximal tubule was examined using free-flow recollection micropuncture techniques. Tubule fluid-to-plasma inulin ratios were measured before, during, and at successive intervals after brief (15-25 sec) intra-aortic injections (at the level of the renal artery) of colloid-free, isoncotic, and hyperoncotic solutions. Arterial hematocrit and protein concentrations were measured simultaneously in these rats. In other rats, total protein concentration of peritubular capillary blood plasma was determined before, during, and after these same infusions with a newly described submicroliter fiber-optic colorimeter. In the 15-25 sec interval necessary to infuse 2 ml of these test solutions, fractional and absolute sodium reabsorption varied directly with peritubular capillary colloid osmotic pressure, declining during infusion of colloid-free solutions, increasing during hyperoncotic infusions, and remaining unchanged during isoncotic infusions. In the subsequent 20-min interval after intra-aortic injection of these test solutions, capillary protein concentration remained at (isoncotic infusions) or returned to (colloid-free and hyperoncotic fluids) control values. Whereas reabsorption after colloid-free solutions returned to base line levels in parallel with the return in capillary protein concentration, after colloid infusions (which resulted in continued expansion of extracellular fluid volume), a progressive decline in reabsorption was observed. These results afford strong evidence that peritubular capillary colloid osmotic pressure is one important determinant of proximal sodium reabsorption. Nevertheless it is apparent that mechanisms other than or in addition to this must be invoked to explain the delayed inhibition of reabsorption that accompanies expansion of extracellular fluid volume by colloid solutions.

Absorption↗
PubMed1968

Micropuncture study of nephron function in the rhesus monkey.

The function of the proximal and distal tubule was studied in the rhesus monkey during antidiuresis and during the diuresis after furosemide administration (during which extracellular fluid volume was maintained).In the proximal tubule, fluid to plasma ratios for sodium, potassium, and osmolality approximated unity. During antidiuresis, about 30% of the filtered water remained at the end of the accessible portion of this segment (92% of length). Fluid was hypotonic to plasma throughout the distal tubule. 25% of the filtered water was present in the early distal tubule. Small but significant water reabsorption (about 8% of filtered) occurred in remainder of this segment. Tubule fluid to plasma potassium concentration ratios tended to increase along the distal tubule, and the amount of potassium, relative to the amount filtered, increased from 13% in the early portion of this segment to 26% in the late portion.After furosemide was administered animals excreted about one-third of the filtered sodium and water. Despite this diuresis, electrolyte and water reabsorption along the proximal tubule did not differ from values obtained in control animals. Osmolality and sodium concentration of fluid from the distal tubule approached those of plasma. 22% of the filtered sodium (twice the control values) reached the distal tubule, whereas the fraction of filtered water remaining was only slightly increased. These findings indicate that, after the administration of this drug, inhibition of sodium reabsorption occurred in the water-impermeable segment of the nephron, rather than in the proximal tubule. After furosemide administration, all tubule fluid to plasma potassium concentration ratios in the distal tubule were equal to or greater than one, suggesting inhibition of active potassium reabsorption at or prior to this site.Fluid to plasma bicarbonate concentration ratios from the midportion of the proximal tubule were consistently less than one in normal monkeys. After acetazolamide was administered, the bicarbonate concentration of samples of tubule fluid recollected from these same sites was the same as, or higher than in plasma. This fact demonstrates the inhibition of bicarbonate reabsorption in this portion of the tubule.

Journal Article↗
PubMed1968

The relationship between glomerular filtration rate and sodium reabsorption by the proximal tubule of the rat nephron.

We have tested two of the hypotheses proposed to explain the adjustment in sodium reabsorption in the proximal tubule that follows a change in the rate of glomerular filtration (glomerulotubular balance). Using the recollection micropuncture technique, we were able to measure the immediate and late changes in reabsorptive rate after an acute alteration in filtration rate produced by aortic constriction and release of constriction. It was found that fractional reabsorption, as measured by the inulin tubule fluid to plasma (TF/P) ratio, increased after aortic constriction and decreased after release, but that in most instances, absolute reabsorptive rate changed in parallel to glomerular filtration rate. The change was similar whether the collections were made less than 1 or more than 5 min after the change in blood pressure. The rapid time course of this adjustment in reabsorptive rate is viewed as evidence against an intrarenal humoral feedback mechanism. In the same experiments we measured the (TF/P)(In), transit time, and flow rate of fluid in single nephrons before and during aortic constriction or release of aortic constriction. The change in reabsorptive rate and the simultaneous change in calculated cross-sectional area of the tubule lumen were rarely proportional, i.e., C/pir(2) was not constant. In other experiments, these same measurements were made before and during periods of increased ureteral pressure. Despite large increments in calculated cross-sectional area, the absolute rate of reabsorption either remained relatively unchanged or fell in proportion to the change in filtration rate. It is concluded that under these conditions, reabsorptive rate is governed by some factor other than tubule geometry.

Animals↗
PubMedDate not supplied

Possible mechanism of prostaglandin-induced renal vasoconstriction in the rat.

We studied the role of the renin-angiotensin system in the vasoconstrictor effect induced by prostaglandins (PG) on the renal microcirculation in 25 euvolemic Munich-Wistar rats. Infusions of subvasodepressor doses of PgE2 and PGI2 led to lower mean values for single nephron (SN) glomerular filtration rate (GFR), total kidney GFR, glomerular plasma flow rate, QA, and ultrafiltration coefficient (Kf) than were found in animals given vehicle alone (control group). On the other hand, the mean values for glomerular transcapillary hydraulic pressure difference, delta P, and total renal arteriolar resistance, RTA, tended to be higher in the experimental groups. The effects of PGI2 on the renal microcirculation were more pronounced than for PGE2. These increases in delta P and RTA and decreases in QA and Kf are typical of changes induced by angiotensin II (AII). To further explore this AII-like phenomenon, an infusion of saralasin, a competitive AII antagonist, was used. Indeed, when saralasin was infused together with either PGE 2 or PGI2 the previously noted effects on delta P, QA, RTA and Kf were largely abolished. Thus, saralasin transformed the renal action of PGE2 and PGI2 from vasoconstrictor (low QA, high RTA) to vasodilator (high QA and low RTA). Therefore, the effects of nonvasodepressor doses of PGE2 and PGI2 on the renal microcirculation appear to depend on an intermediate action of AII.

Animals↗