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Biomedical subjects

A Aperia

Publications and source records attributed to A Aperia.

At least 163 records · Page 9Linked to original sources

Mechanisms for colonic sodium transport during ontogeny: loss of an amiloride-sensitive sodium pathway.

Net colonic sodium and fluid absorption is higher in suckling and weanling rats than in adult rats. This study was undertaken to investigate the mechanisms behind these differences. In vivo perfusion of the colon was performed in 14- to 80-day-old rats. Net Na and water uptake decreased exponentially from 14 to 80 days of age. Na uptake was 402 +/- 73 micrograms Eq/min/g DT in 20-day-old rats and 116 +/- 6 mu Eq/min/g DT in 40-day-old rats. After amiloride treatment, net Na transport was reversed to net secretion (-79 +/- 36 mu Eq/min/g DT) in 20-day-old rats. Amiloride had no effect on the net Na transport in 40-day-old rats. cAMP stimulation significantly increased the net Na uptake in 20-day-old rats and significantly reduced the net Na uptake in 80-day-old rats. cAMP did not increase the net uptake in amiloride-treated 20-day-old rats. We conclude that there are both quantitative and regulatory changes in the pathways for colonic Na transport during development, and we speculate that the large amiloride-sensitive sodium uptake in the young colon is adaptive and contributes to the sodium accretion necessary for rapid growth during late postnatal development.

Aging↗

Development of focal glomerulosclerosis after unilateral nephrectomy in infant rats.

Rats unilaterally nephrectomized in infancy (Nx5) or in adulthood (Nx55) and fed a normal (21%) protein diet were studied at 2, 3 and 6 months after surgery with regard to glomerular filtration rate (GFR) and the development of both albuminuria and focal glomerulosclerosis (FGS) in the remnant kidney. Nx rats were compared with sham-operated animals (S) of corresponding age. The incidence of FGS never exceeded 1.4% in S rats. In Nx5 rats the incidence of FGS was not increased at 2 and 3 months after surgery whereas it was significantly higher (range 10%-27%) than in S rats 6 months after surgery. Urinary albumin excretion was significantly increased in Nx5 rats 2 months after surgery and was even higher 6 months after surgery. In Nx55 rats the incidence of FGS was the same as in Nx5 rats 2, 3 and 6 months after surgery, but urinary albumin excretion was significantly lower than in Nx5 rats 6 months after surgery. The GFR expressed per unit of body weight decreased in both Nx5 and S5 rats from 2 to 6 months, but the decrease was more pronounced in Nx5 rats than in S5 rats. The GFR factored by kidney weight was significantly lower in Nx5 than in any of the other groups at the 6-month follow-up study. We conclude that, as in adults, when unilateral nephrectomy is performed in infancy, FGS will develop in the remnant kidney. More pronounced albuminuria and reduction of GFR may indicate that the glomerular lesion is more severe in rats nephrectomized in infancy than in adulthood.

Aging↗

Partial ureteric obstruction in the pubescent rat. I. Long-term effects on renal function.

A partial obstruction of the left ureter was created in six-week-old rats. The effects on renal function were studied after three, nine and 15 weeks, first in normal hydration, and then after extracellular volume expansion. Moderate hydronephrosis without parenchymal weight reduction developed within three weeks. The hydronephrotic kidney i) excreted during normal hydration less urine and sodium than the intact one, because of increased reabsorption, ii) was capable of reacting fully on volume expansion and iii) had, after volume expansion, a higher renal blood flow and GFR but also a higher reabsorption of water, sodium, potassium and osmoles, resulting in excretions similar to those on the intact side. The differences noted were small (less than 20%) except for sodium excretion. The hydronephrotic kidney seemed to tolerate an increase in ureteral resistance better than the intact one would do. There were no significant differences between the three, nine and 15-week groups, with regard to the effects on the hydronephrotic kidney. Thus, except for a tendency to sodium retention, the effects of partial ureteric obstruction in young rats seem to be relatively harmless and do not increase with time.

Animals↗

Short-term effect of low and high protein intake on renal function in children with renal disease.

The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51-85 ml/min/1.73 m2 BSA) or severely (9-50 ml/min/1.73 m2 BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3-5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m2 BSA and ERPFs above 150 ml/min/1.73 m2 BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.

Adolescent↗

Influence of different protein intake on renal growth in young rats.

We have examined the effect of high protein intake on kidney growth and function in growing rats. The rats were kept on an isocaloric diet containing 12%, 21% and 50% protein, from weaning (16 days) until the time of investigation (18, 20, 24, 40 or 80 days). There was no significant difference between the 12% and 21% protein groups in any of the parameters studied. 50% protein increased body weight (BW) and kidney weight (KW). The increase in kidney weight was already evident after 2 days and exceeded the increase in body weight in all age groups. At 24 days renal cortical DNA and the protein/DNA ratio were significantly increased in the 50% protein group. At 40 days the cortical DNA content, but not the protein/DNA ratio, was significantly increased in the 50% group. The glomerular filtration rate GFR) was studied at 40 days. Total GFR as well as GFR/BW was significantly higher in the 50% group than in the 21% group. In one protocol the diet was discontinued at age 40 days and the rats were studied at age 80 days. In these rats all parameters of renal size and function were the same as in the rats that had had a normal (21%) protein intake from weaning. We conclude that in young rats high protein intake reversibly increases GFR out of proportion to BW and selectively and reversibly stimulates kidney growth by stimulating cell proliferation.

Amino Acids↗

Regulation of serum sodium in dehydrated and orally rehydrated infants. Influence of age and of purging rates.

We have examined the control of serum sodium concentration (S-Na) in 60 male infants with acute diarrheal disease, moderate dehydration, but without the presence of fever, vomiting or other conditions. The infants were studied on admission and during oral rehydration therapy (ORT). We examined the effect of rapid reduction of the purging rate on the control of S-Na by adding pulverized rice and pulses (dal moong) to the rehydration solution. On admission S-Na was significantly inversely related to age. This correlation could not only be attributed to difference in stool sodium losses. Changes in S-Na and urinary K/Na ratio during oral rehydration therapy (ORT), were analyzed separately in infants below and above 4 month of age. During the first six hours of ORT, there was an increase in S-Na in all groups. During the following 18 hours, S-Na tended to normalize around 138 mmol/l. Normalization occurred faster if purging rate was reduced. In all groups urinary K/Na ratio (index of aldosterone production and, inversely, of sodium balance), was high at admission and fell during ORT. In the youngest infants (below 4 month of age) the fall was significantly more pronounced if the purging was reduced. We conclude that it is important to consider age when prescribing ORT. The capacity to correct disturbances in S-Na becomes more efficient during maintenance stage of ORT. Correction of S-Na and sodium balance is enhanced by rapid reduction of abnormal intestinal losses.

Acute Disease↗

The benefits of the very early introduction of powdered rice and dried edible seeds (Dal moong) in the oral rehydration solution during the treatment of acute infectious diarrhoea of infancy.

We have examined whether the addition of powdered rice and pulses (Dal moong) to oral rehydration solution will decrease the purging rate and thereby increase the efficacy of the oral rehydration therapy. The study was carried out on 60 male infants, with acute watery diarrhoea, moderate dehydration but without fever, vomiting, or other conditions like septicaemia and meningitis. The infants were treated with either the standard WHO oral rehydration salt solution (ORS) or with a modified solution where glucose was removed and powdered rice and Dal moong were added. We found that the infants receiving ORS with powdered rice and Dal moong had significantly lower fluid losses in the stools, a significant and more rapid weight gain, and needed significantly less fluid than the infants receiving ORS only.

Acute Disease↗

Role of dopamine2-receptors in mediating renal vascular response to low dose dopamine infusion in the rat.

The effects of the interaction of dopamine (DA) and the DA2-receptors on regional blood flows and cardiac output have been studied in the rat. By means of the microsphere technique the blood flow (BF) and vascular resistance (VR) were determined in the kidney, duodenum, spleen, liver, and lung during infusion of DA in the absence and presence of selective DA2-receptor blockade with S-Sulpiride (S-SP), and during infusion of a selective DA2-receptor agonist (LY-171555, LY). In order to evaluate the role of the presynaptic DA2-receptor, the experiments were performed without alpha- and beta-adrenergic blockade. Dopamine was given in such low doses that stimulation of the adrenergic receptors should be negligible. Dopamine, LY and DA + S-SP did not significantly influence BF and VR in the spleen, liver and lung. Dopamine significantly increased BF and decreased VR in the kidney and the duodenum; LY significantly increased BF in the the kidney but not in the duodenum and decreased VR in both the kidney and the duodenum. In the presence of selective DA2-receptor blockade, DA did not significantly influence BF or VR in the kidney but in the duodenum BF increased and VR decreased to the same extent as in the absence of blockade. In conclusion; the kidney and the intestine are more abundantly supplied with vascular DA-receptors than other organs. In the kidney the interaction between DA and the DA2-receptors significantly contributes the the DA-induced vasodilation. The interaction between DA and the DA2-receptors is of less importance for the DA-induced vasodilation in the intestine.

Animals↗

Effect of L-DOPA, dopamine, dihydroxyphenyl acetic acid and homovanillic acid on Na,K-ATPase activity in rat proximal tubule segments.

We have recently demonstrated that dopamine (DA) inhibits Na,K-ATPase in single proximal tubule (PCT) segments dissected from previously collagenase perfused rat kidney. The aim of the present study was to ascertain whether this effect was directly mediated by DA or if DA was the precursor of an inhibitor. When PCT segments were incubated with L-DOPA, Na,K-ATPase was significantly lower than in vehicle incubated tubules. Inhibition of dopa decarboxylase abolished the effect of L-DOPA on Na,K-ATPase activity. The metabolites of DA, 3, 4-dihydroxphenyl acetic acid (DPAC) and homovanillic acid (HVA) both inhibited Na,K-ATPase activity in doses higher than 10(-6) M. Both HVA and DPAC 10(-4) M caused approximately 35% inhibition. Dopamine inhibited Na,K-ATPase activity even in a dose as low as 10(-7) M. Maximal inhibition (greater than 60%) was found with DA-5 M. Na,K-ATPase activity was significantly lower in tubules exposed to DA 10(-4) and 10(-5) M than in tubules exposed to DPAC or HVA 10(-4) and 10(-5) M. Dopamine produced in proximal tubule cells from L-DOPA, is an active inhibitor of the Na,K-pump in these cells. The DA metabolites DPAC and HVA are less potent Na,K-pump-inhibitors.

3,4-Dihydroxyphenylacetic Acid↗

Dopamine causes inhibition of Na+-K+-ATPase activity in rat proximal convoluted tubule segments.

We studied the effect of dopamine (DA) on Na+-K+-ATPase activity in proximal convoluted tubule (PCT) segments dissected from perfused rat kidneys. DA inhibited Na+-K+-ATPase activity in a dose-dependent manner. Inhibition was significant with 10(-7) M DA and maximal with 10(-4) M DA. The inhibition was reversible. Enzyme inhibition occurred in the presence of DA and a DA antagonist, metoclopramide, but not when 10(5) M of the DA1 and DA2 agonists fenoldopam mesylate and LY 171555 were added in the absence of DA. In PCT segments incubated with the DA precursor dopa, Na+-K+-ATPase activity was also inhibited. However, dopa did not inhibit the sodium pump if dopa decarboxylase activity was blocked with benserazide. These findings suggest an intracellular site of action of DA. In tubules incubated in different K concentrations, 10(-5) DA decreased the maximal activity (Vmax) and increased the Km. DA 10(-5) M caused an almost immediate swelling of PCT segments. Swelling did not occur in the presence of both DA and 10(-5) M amiloride. The DA-induced tubular swelling was probably due to inhibition of Na+-K+-ATPase-mediated Na+-transport. We conclude that in rat PCT segments, DA causes a rapid and reversible inhibition of apparent Na+-K+-ATPase activity and an apparent reduction in the affinity for K. The site of action appears to be intracellular.

Adenosine Triphosphatases↗

A comparative study of size and function of the remnant kidney in patients nephrectomized in childhood for Wilms' tumor and hydronephrosis.

To obtain more information about the natural history of compensatory renal hypertrophy beginning in childhood we traced those who were nephrectomized in childhood for Wilm's tumor (W) and hydronephrosis (Hn) between 1950 and 1978 at one department of surgery in Stockholm. All W patients had received treatment that suppresses cellular division. None of the patients were in renal failure or treated with antihypertensive drugs. All the patients in the follow-up study (22 W, 15 Hn) had a normal contralateral kidney at nephrectomy. Five healthy adults served as controls. The kidney was enlarged in both Hn (142%) and W (125%), but significantly larger in Hn than in W. Renal compensatory growth in W was retarded during the first two years after nephrectomy. The glomerular filtration rate (GFR) was 92% of control in Hn and 82% of control in W. The GFR did not seem to decline with a longer follow-up time in any of the groups. PAH clearance was the same in Hn and W. Albumin excretion was significantly higher in Hn than in W, but not significantly higher in W than in controls. The highest albumin excretion rates were found among the Hn patients with long follow-up time. The results suggest that the large increases in size and function that follow childhood nephrectomy can be blunted by antimitotic agents.

Adolescent↗

Oral rehydration therapy in malnourished infants with infectious diarrhoea.

The clinical response and changes in water and salt homeostasis was studied for 36 hours during oral rehydration therapy with a rehydration solution containing 60 mmol sodium/l (ORS60) in 14 malnourished 3- to 15-month-old Turkish infants with acute infectious diarrhoea. All patients were successfully rehydrated with this treatment. Sodium was efficiently absorbed from the gut and water balance was rapidly restored. Because of excess fluid retention following the initial rehydration period about 50% of the patients became oedematous. Urine volume and urinary sodium excretion were found to be much lower than in well-nourished patients of the same age with acute diarrhoea who were treated in the same way. In all of the malnourished infants the serum sodium level remained within the normal range during treatment. The results show that malnourished infants retain much more fluid and sodium than infants who are in a normal nutritional state. Excessive retention of water and salt seem to be due to an inability of the kidneys to control sodium and fluid homeostasis while orally administered sodium and fluid are being absorbed from the gut. The results show that ORT is safe and efficient in the treatment of malnourished infants with acute diarrhoea. But since these infants run a high risk of developing a severe retention of fluid and salt, and consequently may develop circulatory failure due to hypervolaemia during oral rehydration therapy, it is important to carefully monitor the volume of fluid that is given.

Administration, Oral↗

Ionic transport in individual renal epithelial cells from adult and young rats.

Renal epithelial cells were isolated from the outermost superficial cortex of adult and young rats. The cells, likely of proximal origin, were plated on silicon pieces, and cultured during 1-3 days. Intracellular content and concentrations of K, Na, Cl, and P, and the kinetics of change in intracellular content, after inhibition of Na-K ATPase by incubation with ouabain or in K-free medium, were measured in individual cells in small populations using electron probe analysis. In control medium, concentrations in mM were approximately: K, 130; Na, 15; Cl, 28; P, 140. After 6 h inhibition of Na-K ATPase, cells exchanged all K for Na, and the intracellular Na concentration increased to 139 mM in K-free medium. The Cl concentration increased at most to 46 mM. The sum of intracellular K + Na + Cl did not increase more than 25% after 24 h incubation in K-free medium. There were no differences in intracellular K, Na, and Cl for adult and young rat cells in similar conditions. The half-times of K efflux and Na influx after inhibition of Na-K ATPase measured in adult rat were approximately 16-20 min. In the absence of serum, in K-free medium, the half-times of K efflux and Na influx in young rat cells were approximately 30 min, significantly higher than the half-time in the presence of serum, and with ouabain, being approximately 13 min. Histograms of distributions of K and Na content showed that the cells behaved as a single functional population. Ouabain Ki was estimated to be 10(-4) M. After 24 h preincubation in K-free medium, when returned in 5 mM K-containing medium, adult rat cells recovered rapidly normal intracellular K and Na concentrations. Using this approach, expression of the kinetics ionic transport properties of renal epithelial cells during development, and the hormonal influences on terminal differentiation may be studied.

Age Factors↗

Studies of the renal component of the hypertension in rats with aortic constriction. Role of angiotensin II.

The object of this study was to investigate the renal component of hypertension in aortic constriction. In 40-day-old Sprague-Dawley rats the aorta were constricted either proximal (PAC) or distal (DAC) to the renal arteries. The rats were examined 3 weeks later together with control rats. The arterial pressure proximal to the constriction was elevated in the PAC group but not in the DAC group. In PAC rats the arterial pressure was also elevated distal to the constriction. There was a significant pressure gradient across the constriction in both PAC and DAC rats. The PAC rats had a significant decrease of renal blood flow, a significant increase in renal vascular resistance and a numerical but not significant decrease of glomerular filtration rate. Serum levels of angiotensin II were not significantly different in PAC and control rats. The pressor effect of a bolus dose of angiotensin II was significantly increased in PAC rats. Captopril, a converting enzyme inhibitor, decreased the arterial pressures and renal vascular resistance in PAC rats. The pressure elevating effects of angiotensin II and pressure lowering effect of captopril were more pronounced distal than proximal to the constriction. We conclude that the kidneys play a major role in the development of hypertension in PAC, and that the local effect of angiotensin II on the renal vascular bed is an important contributor to the renal component of the hypertension.

Angiotensin II↗

Role of arginine-vasopressin for the development of hypertension following aortic constriction.

This study concerns the role of arginine-vasopressin (AVP) for the development of hypertension after constriction of the abdominal aorta proximal to the renal arteries (PAC). The PAC was applied in AVP-deficient Brattleboro (Bb) rats and the blood pressure was recorded 3 weeks later. In untreated rats, PAC did not cause hypertension. When the rats were given AVP 0.6 or 6 nmol day-1 for 2 weeks using mini-pumps, hypertension developed both proximal and distal to the constriction. The level of the hypertension was independent of the AVP dose. When the rats were given I-deamino-4-valine-8-D-arginine-vasopressin (dVDAVP) a specific antidiuretic agonist without effect on the vascular AVP receptors, hypertension did not develop. Sham-operated rats given AVP did not develop hypertension. The PAC rats treated with AVP but not with dVDAVP had an enhanced pressor response to an i.v. bolus dose of angiotensin II. It is concluded that AVP plays an important role in the development of hypertension following aortic constriction and that the action is mediated via the vascular AVP-receptors. We suggest that the presence of AVP permits the expression of other hypertensive factors, such as angiotensin II.

Angiotensin II↗

Studies on final differentiation of rat renal proximal tubular cells in culture.

The ontogeny of effective Na and K permeability has been studied in renal epithelial cells isolated from the outermost superficial cortex from adult and young (10-15 days) rats. The cells were cultured for 2-4 days and exhibited phloridzin-inhibitable alpha-methylglucoside uptake, characteristic of renal proximal tubular cells (RPTC). Intracellular concentrations of K, Na, Cl, and P and kinetics of changes in intracellular ionic content after inhibition of Na-K-ATPase with 1 mM ouabain (or by incubation in low-K medium) were measured in individual cells using electron probe analysis. Intracellular concentrations of K, Na, Cl, and P were equivalent in young and adult rat RPTC. Adult rat and young rat cells preincubated in K-free medium rapidly recovered normal intracellular K and Na contents when returned to 5.5 mM K medium. The recovery was almost immediately blocked by ouabain. Effective permeabilities measured as half time of K efflux and Na influx after ouabain inhibition of Na-K-ATPase were higher in adult than in young RPTC cultured for less than 4 days. Effective K and Na permeabilities decreased significantly with increasing time in culture in adult but not in young rat RPTC. Among young rat RPTC, half times of Na and K fluxes were significantly correlated to age. Effective K and Na permeabilities were lower in both young and adult rat RPTC that had been serum deprived for 24 h than in cells that had been continuously cultured in serum. In cells cultured for 3 days and serum deprived for 1 day, the addition of serum significantly increased K and Na permeability both in young and adult RPTC, but the effect was more pronounced in young RPTC where permeability reached the same high values as in adult RPTC continuously cultured in serum. In conclusion, effective Na and K permeabilities and serum activation of "permeability units" change during ontogeny. These ontogenic changes might be blunted after a few days in culture due to dedifferentiation of adult rat RPTC.

Aging↗