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B Corman

Publications and source records attributed to B Corman.

At least 73 records · Page 4Linked to original sources

Urinary kallikrein excretion in normotensive aging female rats.

The effect of aging on the intrarenal kallikrein-kinin system activity was investigated in normotensive 3-, 10-, 20-, and 30-month-old female Wistar rats. Urinary kallikrein excretion was measured by three independent assays (immunoreactive concentration, kininogenase, and amidolytic activities) and was found to decrease progressively from 10 to 30 months. In the 30-month-old rats the urinary immunoreactive kallikrein excretion represented 40-44% of the level detected in 3-month-old rats. Active and total kallikrein exhibited the same magnitude of reduction. Furthermore, the active to inactive kallikrein ratio remained unchanged throughout the life period studied. The level of urinary kallikrein inhibitor was studied by measuring the recovery of purified rat urinary kallikrein added in the samples; no change was observed with aging. None of the factors known at present to influence kallikrein excretion could be evoked to explain this age-related decrease. It is therefore suggested that this decrease may reflect a progressive impairment of the intrarenal endocrine function or an alteration in the secretion of the enzyme.

Aging↗

Determination of solute reflection coefficients in kidney brush-border membrane vesicles by light scattering: influence of the refractive index.

Solute reflection coefficients sigma of cell membrane vesicles or liposomes are commonly determined by comparison of the water flow induced by a gradient of the studied solute and that of a reference molecule using light scattering techniques. However, variations in scattered light which are mainly related to change in vesicle volume are also influenced by the refractive index of the surrounding medium. Therefore comparing kinetics of vesicle shrinkage induced by hyperosmotic solutions which have different refractive indexes might lead to an under or over estimation of sigma. We determined sigma NaCl in rat kidney brush-border membrane vesicles by two different approaches using mannitol, a poorly permeant molecule, as reference. (1) The refractive index of the hyperosmotic NaCl solution was adjusted to that of mannitol by addition of polyvinyl pyrrolidone (Mr 40,000), without a significant increase in osmolality. Thereby the change in scattered light intensity induced by osmotic vesicle shrinkage due to gradients of NaCl and mannitol were comparable and led to a sigma NaCl value close to one instead of the previously published value of 0.53. (2) The reflection coefficient was calculated from the lifetime of vesicle shrinkage which is not refractive index-dependent. Again sigma NaCl was not different from one. These results suggest that the water proteic pathways found in the luminal membrane of proximal tubules are not shared by salts.

Animals↗

Myocardial effect of converting enzyme inhibition in hypertensive and normotensive rats.

The effects of converting enzyme inhibition on the cardiac mass, isomyosins polymorphism, and collagen network in the left ventricle have been studied in renovascular, hypertensive, spontaneously hypertensive, and normotensive rats. The isoenzyme profile of left ventricular myosins was used as an indirect marker of the intrinsic property of contractility, whereas the collagen network, measured by a morphometric method, represented an indirect structural marker of the arrhythmogenic risk. One-clip, two-kidney renovascular hypertension was associated with cardiac hypertrophy, a shift in the isomyosin profile, and accumulation of collagen within the left ventricular myocardium. In this renin-angiotensin-dependent model, one month of treatment with converting enzyme inhibitor normalized blood pressure and consistently reversed cardiac hypertrophy and the isomyosin profile. Converting enzyme inhibitor treatment of 12-week-old spontaneously hypertensive rats for three months significantly decreased blood pressure but did not completely normalize it. The increase in cardiac mass observed in spontaneously hypertensive rats was not reversed by this short treatment. Nevertheless, the percentage of the V1 form of myosin increased slightly after treatment, and the collagen content of the left ventricle was considerably decreased. Converting enzyme inhibition did not decrease blood pressure in DOCA-salt hypertension, and no changes were observed in cardiac hypertrophy, isomyosin profile, or the collagen network. The cardiac hypertrophy that occurs with aging in normotensive rats was associated with a significant shift in isomyosin profile and a large accumulation of collagen. Thus, aging mimics several of the quantitative and qualitative changes in the left ventricular protein profile observed in hypertension. In young normotensive rats, converting enzyme inhibition significantly decreased blood pressure and left ventricular mass, increased the percentage of V1 isomyosin, and prevented the accumulation of collagen. In one-year-old normotensive rats, treatment for six months with converting enzyme inhibitor decreased blood pressure, decreased cardiac mass, and prevented the accumulation of collagen; the isomyosin profile was not modified. Converting enzyme inhibition, by acting on cardiac afterload, can bring about quantitative and qualitative changes in the cardiac proteins of both hypertensive and normotensive rats.

Aging↗

Effect of feeding on glomerular filtration rate and proteinuria in conscious aging rats.

Food intake increases glomerular filtration and proteinuria in adult rats. That this postprandial hyperfiltration could be age dependent was investigated in 3-, 10-, 20-, and 30-mo-old rats. Glomerular filtration rate and protein excretion were measured in fed or 24 h fasted conscious animals. In the 3-mo-old rats food ingestion increased renal filtration by 45% from 1.17 +/- 0.08 to 1.73 +/- 0.11 ml.min-1.g kidney wt-1 (n = 6). As the animals became older, the differences between fed and fasted periods became smaller: in 30-mo-old rats glomerular filtration rate was 0.85 +/- 0.03 and 1.01 +/- 0.06 ml.min-1.g kidney wt-1 (n = 6) in fasted and fed conditions, respectively. Proteinuria, which was mainly albuminuria, increased slightly with age and was more markedly reduced by acute food restriction in the 30-mo-old than in the 3-mo-old rats. Because the renin-angiotensin system activity decreases with age, its role in postprandial hyperfiltration was assessed by measuring glomerular filtration in 3-mo-old animals whose angiotensin II converting-enzyme activity was chronically inhibited by daily administration of perindopril. In such experimental conditions there was no longer a difference in renal filtration between fed and fasted rats. These data indicate that 1) postprandial increase in glomerular filtration is to some extent related to the renin-angiotensin system activity; 2) short-term reduction of food intake reduces proteinuria even in senescent rats, although the feeding dependence of the glomerular filtration is blunted with age.

Animals↗

Interdependence of food intake and angiotensin converting enzyme inhibition on kidney function.

Acute or chronic inhibition of angiotensin converting enzyme (ACE) activity in normotensive rats may increase, decrease or cause no change in renal blood flow. Since renal blood flow and the glomerular filtration rate are highly dependent on protein intake, we investigated the question of whether the reported differences in the renal effects of ACE inhibition can be explained by the level of food intake. Glomerular filtration and arterial pressure were measured in conscious, chronically catheterized rats, which were either fed or fasted for 24 h on the day of experiment. In the control group, the glomerular filtration rate was 45% higher in fed than in fasted rats, while blood pressure and plasma renin concentration were unchanged. In experimental animals, given daily 1-mg/kg doses of the ACE inhibitor perindopril, the glomerular filtration rate was the same in both fed and fasted animals and comparable to the values of fasted control animals. Mean blood pressure was reduced from 113 to 91 mmHg by perindopril. It is concluded that chronic ACE inhibition prevents postprandial hyperfiltration and decreases the blood pressure of fed or fasted rats by 20 mmHg, but does not affect renal function in fasted rats.

Angiotensin-Converting Enzyme Inhibitors↗

Cholesterol content and water and solute permeabilities of kidney membranes from aging rats.

The influence of the age-related increase in cholesterol content of kidney brush-border membranes on their water and solute permeabilities was studied in 10- and 24-mo-old male Wistar rats. These permeabilities were determined from the rate of shrinkage and swelling of brush-border vesicles using a stopped-flow apparatus coupled to a light transmission recording. Despite a 20% rise in total cholesterol per milligram proteins, the osmotic water permeabilities of the vesicles were unchanged between 10 (287 +/- 40 micron/s) and 24 mo (270 +/- 31 micron/s). In contrast, passive diffusions of NaCl and KCl, but not of urea, thiourea, and glycerol, were reduced by 35% between 10 and 24 mo. These results suggest that an increase in cholesterol content of kidney brush-border membrane decreases its salt permeabilities without altering the water pathways.

Aging↗

Glomerular filtration, renal blood flow, and solute excretion in conscious aging rats.

Measurement of daily food and water intakes and of renal water and solute excretion in 10-, 20-, and 30-mo-old female rats revealed that they ate the same amounts of food and excreted the same amounts of glucose, sodium, and potassium irrespective of age but that in the 30-mo-old rats phosphate, calcium, and magnesium excretion rose. The glomerular filtration rate and p-aminohippuric acid clearance measured in conscious animals following moderate volume expansion did not differ with age, when expressed per 100 g body wt, but decreased markedly in the 30-mo-old rats when compared with kidney weight. This was related to the senile hypertrophy of the kidneys in the 30-mo-old group, which was reflected by increases in glomerular volume and length of the proximal tubules and by enlargement of the medulla, with the number of nephrons remaining constant with age. There was no evidence of glomerulosclerosis or kidney disease, and proteinuria remained at a low level in all three age groups. These results suggest that the diminished renal filtration rate observed in both conscious and anesthetized senescent rats is due to a reduced supply of blood per gram of kidney tissue and not to loss of nephrons.

Aging↗

Osmotic water permeability and solute reflection coefficients of rat kidney brush-border membrane vesicles.

Solute reflection coefficients, sigma i, of rat kidney brush-border membrane vesicles were determined by the comparison of water flows induced by equiosmolal gradients of sucrose and NaCl, KCl or mannitol. The values of 0.53 for sigma NaCl and 0.56 for sigma KCl when compared with 0.92 for sigma mannitol suggested some interactions between salt and water pathways. Altering the membrane proteins with 0.4 mM HgCl2 decreased the osmotic water permeability of the vesicles by 70 to 80% and brought sigma NaCl and sigma KCl to a value not different from 1. This argued in favor of water protein pathways in the luminal membrane of kidney proximal cells which are partly accessible to NaCl and KCl.

Animals↗

Evidence for proteic water pathways in the luminal membrane of kidney proximal tubule.

The osmotic permeability of the apical membrane of proximal tubule cells was studied on rat brush-border membrane vesicles by following their rate of shrinkage with a stopped-flow device coupled to light transmission recording. The mercuric sulfhydryl reagent para-chloromercuribenzenesulfonic acid (PCMBS) reduced the water permeability of the membrane, in a time- and dose-dependent manner, to 35% of the control value. Mercuric chloride was a more potent inhibitor and decreased the osmotic water permeability of the brush-border membrane to 15% of the control. This inhibition was reversed by an excess of cysteine, while cysteine per se did not modify the rate of vesicle shrinkage. These results suggest that most of the osmotic water movements across kidney brush-border membranes are through polar pathways which involve the integrity of the membrane proteins.

4-Chloromercuribenzenesulfonate↗

Renin-angiotensin system, converting-enzyme inhibition and kidney function in aging female rats.

The age-related changes in the renin-angiotensin system were investigated in normotensive 3-, 10-, 20-, and 30-mo-old female Wistar rats. Plasma renin concentration and immunofluorescent renal renin index remained constant from 3 to 10 mo, then decreased as the animals become older, whereas plasma concentration of renin substrate diminished slightly between 10 and 20 mo and plasma converting-enzyme activity was not modified with age. Acute inhibition of converting-enzyme activity by intravenous administration of 0.1 mg/100 g body wt S 9780 (the diacid form of S 9490) was followed by a 7- to 8-mmHg decrease in arterial pressure and a concomitant 10-12% increase in inulin and p-aminohippuric acid (PAH) clearance in the 10- and 20-mo-old rats. On the other hand, neither glomerular filtration rate, PAH clearance nor arterial blood pressure were affected by converting-enzyme inhibition in the 30 mo-old rats. These results indicate that the activity of the renin-angiotensin system is progressively reduced with age and suggest that angiotensin II does not play an important role in the maintenance of blood pressure and kidney hemodynamics in normotensive female senescent rats.

Aging↗

Age-related changes in enzyme activities, protein content and lipid composition of rat kidney brush-border membrane.

Age-related changes in enzyme activities, protein electrophoretic patterns and lipid composition of kidney-brush-border membranes were studied in 10-20- and 30-month-old male and female Wistar rats. Polyacrylamide gel electrophoresis of membrane proteins revealed very little changes with increasing age, whether males or females were considered. The Km of three hydrolases - maltase, L-aminopeptidase and alkaline phosphatase - were not affected by age while the Vmax of maltase and alkaline phosphatase, but not of L-aminopeptidase, decreased from 10 to 30 months. The phospholipid to protein ratio which remained constant between 10 and 20 months, rose in both sexes from 20 to 30 months. In males, the cholesterol content of the membrane increased faster than that of phospholipid and the cholesterol over phospholipid ratio was then greater at 30 months than at 10 months, while in females this ratio remained unchanged in the course of aging. The fatty acid composition of the brush-border remained more or less constant with age in female rat whereas in the male, a 10% decrease in the proportion of arachidonic acid from 10 to 30 months was responsible for a lower unsaturation index.

Aging↗

Streaming potentials and diffusion potentials across rabbit proximal convoluted tubule.

The streaming potential, defined as the transepithelial potential appearing in the presence of an osmotic water flow, was measured in rabbit kidney proximal convoluted tubules perfused in vitro. The S2 segments studied were dissected from mid-cortical and juxtamedullary portions of the kidney and the streaming potential induced by the addition of raffinose in bath was compared for each tubule with the diffusion potential corresponding to an imposed NaCl gradient in the absence of osmotic gradient. The amplitude of the measured streaming potential was found to vary from positive to negative values (+0.9 to -1.8 mV) according to the location of the dissected tubule: the more juxtamedullary the nephron, the more lumen negative was the streaming potential. This correlated well with the diffusion potentials recorded on the same tubules and the amplitude of the streaming potentials was a close function of the PNa/PCl ratios calculated from these diffusion potentials. This is in agreement with the hypothesis of solute polarization in an unstirred layer as the origin of the streaming potential; a calculation of hydraulic permeability (Pf) of the proximal tubule, taking the role of such an unstirred layer into consideration is proposed.

Animals↗

Changes in anatomy, glomerular filtration, and solute excretion in aging rat kidney.

Changes in kidney function were studied in anesthetized female WAG/Rij rats 6, 18, and 30 mo old. The growth in kidney size measured between 6 and 18 mo and 18 and 30 mo was due to enlargement of the glomeruli and lengthening of the proximal tubules, without significant changes in the number of nephrons. Glomerular filtration per gram kidney was unaffected between 6 and 18 mo but diminished 27% between 18 and 30 mo. This reduction was accompanied by an intrarenal redistribution of individual filtration rates for the superficial and deep nephrons. Fractional excretion of sodium, potassium, calcium, and magnesium declined sharply between 6 and 18 mo but did not change further between 18 and 30 mo, whereas the fractional excretion of amino acids and glucose remained constant between 6 and 18 mo but rose in the 30-mo group. Taken together, these observations indicate that, in the rat, kidney aging cannot be reduced to a loss in the number of functional nephrons but is the result of several differential and specific processes.

Aging↗

Fluid composition of basolateral space of kidney cells in culture and its modification by intracellular cAMP.

LLC-PK1 kidney cells, like other epithelial cells, form domes due to Na+ and water movements from the apical to the basolateral side of the epithelium when cultured on a nonpermeable support. The composition of the fluid trapped under these domes can therefore be considered to reflect the nature of the fluid reabsorbed through the epithelium. Collecting the basolateral fluid by micropuncture and analyzing it by electron microprobe revealed that it was isosmotic with the external medium and that the concentrations of Na+, Cl-, Ca2+, Mg2+, and phosphate were nearly the same in both. In contrast, the K+ concentration was found to be 40% lower under the domes than in the bath. Changing the osmolality of the apical medium showed that the epithelium was leaky for water, although it maintained an ionic gradient for at least 20 min. Fifteen minutes after addition of dibutyryl adenosine 3',5'-cyclic monophosphate or 3-isobutyl-1-methylxanthine (5 X 10(-4) M) to the external medium, the phosphate concentration in the basolateral fluid was increased. This rise peaked at 1 h and diminished thereafter. The significance of these observations is discussed in regard to transepithelial permeability and to the transport properties of LLC-PK1 cells.

1-Methyl-3-isobutylxanthine↗

Volume expansion modulates NaHCO3 and NaCl transport in the proximal tubule and Henle's loop.

The effects of extracellular fluid volume expansion on kidney reabsorption of bicarbonate, chloride, and water were examined in Sprague-Dawley rats by paired micropuncture experiments in which tubular fluid was collected from early distal and end-proximal sites. In group I, rats were studied during a plasma-replete euvolemic state and after 10% body wt colloid-free volume expansion. The filtered loads were similar in euvolemia and expansion; expansion increased end-proximal total CO2 concentration ([tCO2] EP) from 13.0 +/- 0.8 to 18.4 +/- 0.7 mM and inhibited the tCO2 fractional reabsorption 26% in the proximal convoluted tubule and 15% in Henle's loop. Early distal tCO2 delivery therefore increased from 61 +/- 7 to 140 +/- 17 pmol X min-1 X g kidney wt-1. A more pronounced inhibition of fractional reabsorption of chloride (45%) and water (35%) occurred in the proximal convoluted tubule during expansion. In group II, rats were studied during 5% body wt 70 g/liter albumin-containing expansion and after 10% body wt colloid-free expansion. Compared with euvolemia of group I, albumin expansion decreased proximal fractional reabsorption of tCO2 13%, chloride 19%, and water 14% without change in filtered loads, and [tCO2]EP rose to 17.2 +/- 0.7 mM. A 10 g/liter decrease in plasma protein concentration during colloid-free expansion was associated, compared with albumin expansion, with inhibition of proximal fractional reabsorption of tCO2 by 4%, chloride by 18%, and water by 9% without further altering [tCO2]EP. We conclude that 1) expansion specifically inhibits bicarbonate reabsorption in the proximal convoluted tubule and in Henle's loop independent of change in filtered load or in peritubular protein concentration, probably by enhancing bicarbonate backdiffusion and reducing proton secretion; 2) expansion-induced decrease in peritubular protein concentration contributes to the proximal expansion effect probably by specifically inhibiting transcellular sodium chloride reabsorption.

Animals↗

Does water drag solutes through kidney proximal tubule?

Coupling of salt and water movements across kidney proximal tubules was studied in the presence of an induced transepithelial osmotic water flux. Convoluted proximal tubules from rabbit kidney were perfused in vitro with a control solution, with or without 50 mM/l of mannitol or raffinose in the both. Osmolalities of the perfused and collected fluids as well as the net water flux Jv were measured in each experiment. The net solute flux Js was calculated from the difference between the amount of total solutes delivered and collected at each end of the tubule. No apparent net transepithelial solute movements were detected in the presence of an osmotic water flux when active solute transport was inhibited either by an external to of 26 degrees C or by ouabain in the bath. The water flux observed was similar to that calculated assuming that only water crossed the epithelium, and no streaming potential was measured, whether or not active transport was blocked. It is concluded that the osmotic water flux through kidney proximal tubule does not drag a significant amount of solutes, probably because of the absence of convective solvent flux. This suggests the existence of different pathways for water and salt movement.

Animals↗

Stimulation by antidiuretic hormone of electrolyte tubular reabsorption in rat kidney.

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on renal excretion and tubular transport of water and electrolytes were investigated in homozygous DI Brattleboro rats. To ascertain these effects on the loop of Henle, circulating glucagon, parathyroid hormone, and thyrocalcitonin were reduced before the experiments, as these hormones are believed to stimulate the same cells of the thick ascending limb as ADH. dDAVP did not alter either glomerular or proximal tubular functions. In the loop, it consistently raised reabsorption of Mg, Ca, K, and, to a lesser extent, Na and Cl, but phosphate transport was not affected. dDAVP lowered the urinary excretion rates for Mg, Ca, K, Cl, and total solutes. For Mg, this reduction was independent of the drop in the urinary flow rate following dDAVP administration but was significantly correlated to this drop in the case of Ca, K, Cl, and total solutes. Na and P excretions were not altered by dDAVP. It is concluded that, in vivo, administration of ADH 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, 2) consistently enhances Mg reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle, and 3) at maximal antidiuresis, raises Ca, K, Cl, and total solute reabsorption, probably because of the drop in tubular flow rates in the distal parts of the nephron consequent to the hormone administration.

Animals↗

Dependence of water movement on sodium transport in kidney proximal tubule: a microperfusion study substituting lithium for sodium.

The relationship between water and sodium movements through the mammalian proximal convoluted tubule was investigated by substituting lithium for sodium. Proximal convoluted rat Kidney tubules were perfused in vivo with a Ringer solution containing 107 meq/liter lithium and 42 meq/liter sodium. Several micropunctures were made along the same nephron, and [3H] inulin, [14C] glucose, 22Na, osmolality, Na, Mg and Cl were determined on each sample. Measurements of 22Na showed that sodium and lithium diffusion rates were practically identical throughout the entire epithelium. A one- for-one exchange of sodium for lithium induced a negative transepithelial net flux of Na from plasma to lumen. However, despite this negative flux, a positive net water movement was measured from lumen to plasma. This movement was proportional both to glucose reabsorption and to the rise in the chloride concentration, two mechanisms known to be dependent on the transcellular movement of sodium. It was therefore concluded that the net water flux was a function of the unidirectional transcellular net flux of Na. Rabbit proximal convoluted tubules were perfused in vitro with solution containing 75 meq/liter Li and 75 meq/liter Na on both the luminal and peritubular sides. Under these conditions, the water reabsorption rate dropped to half its control value. Water movement was therefore a function of the external sodium concentration, which in turn probably regulates the intracellular Na concentration.

Animals↗