Search PubMed⌕ Search

Biomedical subjects

A Aperia

Publications and source records attributed to A Aperia.

At least 127 records · Page 7Linked to original sources
PubMed1990

Enalapril reduces microalbuminuria in young normotensive type 1 (insulin-dependent) diabetic patients irrespective of its hypotensive effect.

The effect of enalapril on albumin excretion rate was studied in two groups of age- and sex-matched Type 1 (insulin-dependent) diabetic patients, aged 15-20 years, with persistent microalbuminuria greater than 20 micrograms/min. Group 1 contained six patients with systolic blood pressure greater than or equal to 75th percentile for age and sex, group 2 six normotensive patients. Enalapril (10-20 mg/day) was given for six months. Albumin excretion rate, glomerular filtration rate, renal plasma flow, blood pressure at rest and during exercise, and angiotensin converting enzyme activity were measured before, after three weeks' and six months' treatment and six months after treatment withdrawal. Albumin excretion rate decreased in all patients after three weeks' (mean decreases 55% in group 1, 65% in group 2) and six months' treatment (35% in group 1, 61% in group 2). Systolic blood pressure remained unchanged in both groups. Diastolic pressure was reduced after three weeks in group 1 (p = 0.001). No reduction in increment in systolic pressure during exercise test occurred in any group during treatment. Angiotensin converting enzyme activity decreased in all patients after three weeks (p = 0.001) and six months (p = 0.003). This correlated to the decrease in albumin excretion rate after three weeks (r = 0.79, p = 0.05) and six months (r = 0.59, p = 0.04). HbA1c, mean blood glucose and glomerular filtration rate remained unchanged during the study in both groups. Renal plasma flow tended to increase after three weeks' and six months' treatment in group 2 (p = 0.06, respectively) but not in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

99mTechnetium dimercaptosuccinic acid scintigraphy in the diagnosis of acute pyelonephritis in rats.

The use of 99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) scintigraphy for the early diagnosis of pyelonephritis has been evaluated in a study performed on adolescent female Sprague-Dawley rats exposed to an ascending Escherichia coli infection. The rats were studied with DMSA scintigraphy either before and 5 days after the infection or 5 and 28 days after the infection. One group of rats received anti-microbial treatment during days 6-11. After the last DMSA scintigraphy the rats were sacrificed and the kidneys prepared for light microscopy study. Kidney morphology was normal and DMSA uptake was high and homogeneous in all control rats. The majority of the rats exposed to E. coli developed inflammatory changes, on light microscopy which extended to various degrees in the renal parenchyma. Five days after the infection the DMSA uptake was consistently reduced, if the inflammatory lesion on light microscopy involved more than 15% of the renal cortex. Twenty-eight days after infection the inflammatory changes were less extensive than at 5 days. The DMSA uptake had usually improved. At this time, however, areas of decreased DMSA uptake could be detected even if the light microscopy changes involved less than 15% of the parenchyma. Microscopical lesions were less frequent and less extensive in the treated than in the untreated rats. The complete return to normal of previously abnormal DMSA uptake was only observed in treated rats. In a few untreated rats cortical scars had formed by day 28. The scars appeared in areas with decreased DMSA uptake at 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

The significance of L-amino acid decarboxylase and DARPP-32 in the kidney.

This study examines the role of endogenous dopamine (DA) for the regulation of renal tubular sodium (Na) transport. The enzyme L-amino acid decarboxylase (L-AADC) that converts L-dopa to DA has been localized to the proximal tubule cells with immunocytochemistry. Locally formed DA will inhibit the activity of Na-K-ATPase, the enzyme that yields energy to active Na transport. The effect is of physiological importance during high salt diet. The phosphoprotein DARPP-32, a DA1 receptor associated third messenger is abundant in the medullary thick ascending limb of Henle (mTAL). DARPP-32 is phosphorylated after activation of DA1 receptors. DARPP-32 is in its phosphorylated form a potent phosphatase inhibitor. Activation of the DA1 receptor in mTAL with the DA1 agonist SKF 82526 causes dose-dependent inhibition of Na-K-ATPase activity. The effect involves activation of cAMP protein kinase. It is likely that this effect is potentiated by DARPP-32.

Animals↗
PubMed1990

Short-term regulation of Na+,K(+)-ATPase activity by dopamine.

The short term regulation of the activity of the Na,K-pump (Na+,K(+)-ATPase) is just beginning to be understood. By using single microdissected proximal tubule segments (PCT) (permeabilized in order to clamp Na entry), it was possible to study regulation of Na+,K(+)-ATPase activity in its own environment and in a well defined cell population. The Na+,K(+)-ATPase activity can be regulated over a short term via guanidine triphosphate (GTP) dependent regulatory proteins. However the guanidine proteins are not directly coupled to the Na,K-pump and the mechanism involves the activation of complex intracellular signalling system. Locally produced dopamine induces a dose dependent inhibition of Na+,K+ ATPase activity. This inhibition is mediated by a complex mechanism that requires the activation of both membrane dopamine receptors, DA-1 and DA-2. It involves the activation of a pertussis toxin sensitive GTP-binding protein and activation of protein kinase C. A DA-2 agonist only inhibits Na+,K(+)-ATPase activity when it is incubated together with dibutyryl cAMP or Forskolin. We have therefore concluded that an increase in cellular cAMP levels plays a permissive role for DA-2 inhibition of Na+,K(+)-ATPase activity. A fully differentiated cell is required for dopamine inhibition of Na+,K(+)-ATPase activity. An abnormal regulation of proximal tubule Na+,K(+)-ATPase activity might be of importance in the pathogenesis of certain types of hypertension.

Animals↗
PubMed1990

Tubular response to hormones is blunted in weanling rats.

The renal responses to atrial natriuretic peptide (ANP), parathyroid hormone (PTH) and arginine vasopressin (AVP) were studied in anaesthetized weanling and adult rats with clearance methods. In rats receiving PTH, thyroparathyroidectomy (TPTX) was performed prior to the study. The results showed that GRF remained unchanged in both age groups during infusion with ANP, AVP and PTH after TPTX as well as with TPTX alone. During ANP infusion, the urine flow rate increased from 0.01 +/- 0.002 to 0.029 +/- 0.004 ml (100 g body wt)-1 min-1 (P less than 0.001) and the fractional sodium excretion increased from 0.48 +/- 0.1 to 3.0 +/- 0.4% (P less than 0.001) in the adult rats; no significant changes were observed in the weanling rats. Phosphate excretion was not influenced by ANP in either age group. After TPTX, both net and fractional phosphate excretion decreased in both age groups. During PTH infusion in TPTX rats, both net and fractional phosphate excretions increased significantly in the adult rats but were unchanged in the weanling rats. In rats of the same age, the renal concentrating capacity and urinary excretion of prostaglandin E2 (PGE2) were determined after dehydration. The renal concentrating capacity was lower, and the renal excretion of PGE2 was higher, in the weanling than in the adult rats. Furthermore, the concentrating mechanism seems not to be influenced by indomethacin treatment in either age group. It is concluded that the tubular responses to ANP and PTH are blunted in the immature kidney and that the renal excretion of PGE2 is not an important factor in the regulation of the concentrating capacity in the weanling rat.

Animals↗
PubMed1990

High protein intake accelerates the maturation of Na,K-ATPase in rat renal tubules.

UNLABELLED: We have examined the effect of a high protein intake on renal maturation by studying the Na,K-ATPase activity in proximal convoluted tubules (PCT) and medullary thick ascending limb of Henle (TAL) in kidneys from 16- to 24-day-old rats. The rats received an isocaloric diet containing 21% (normal protein, NP) and 50% (high protein, HP) protein from 16 days of age. HP diet significantly increased the nephron filtration rate after 2 days. There was a proportionate increase in proximal tubular reabsorption. HP diet significantly increased Na,K-ATPase in both PCT and TAL after 4 days, but not after 2 days. Although HP diet caused a similar increase in Na delivery to PCT and TAL, the increase in Na,K-ATPase activity after 8 days was more pronounced in TAL than in PCT. To determine whether stimulation of Na,K-ATPase required the presence of adrenal corticoid hormones, rats adrenalectomized at 16 days of age were studied. HP diet significantly increased Na,K-ATPase in both PCT and TAL from adrenalectomized rats. To determine whether stimulation of Na,K-ATPase in PCT was mediated by increased Na entry via the amiloride-sensitive Na/H exchanger, rats were treated with amiloride via an osmotic minipump from 16 to 20 days of age. Amiloride treatment significantly retarded the normal increase of Na,K-ATPase in NP rats but had no effect on ouabain-insensitive ATPase. HP diet significantly increased PCT Na,K-ATPase, in spite of chronic amiloride treatment. CONCLUSION: HP intake accelerates maturation of Na,K-ATPase in PCT and TAL regardless of the presence of adrenal corticoid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1990

Amino acid stimulation of Na,K-ATPase activity in rat proximal tubule after high-protein diet.

Ouabain-sensitive (OS) O2 consumption was determined in proximal tubular cells from weanling rats fed 21% (normal-protein, NP) or 50% (high-protein, HP) protein diet for 4 days. Butyric acid 10(-3)M was added as a substrate for mitochondrial respiration and the ionophore amphotericin B (10 micrograms ml-1) was used to sodium-load the cells. OS respiration was higher in HP than in NP cells in both DME and amino acid-free electrolyte solution (ES). Amphotericin B significantly increased OS respiration in both NP and HP cells, implying that the Na-K pump was activated by increased intracellular Na. In cells incubated in ES, addition of amino acids stimulated OS respiration significantly in HP cells (16.9 +/- 1.4 vs 21.2 +/- 1.1 nmol min-1 mg-1 protein) and in NP cells (13.9 +/- 0.3 vs 14.9 +/- 0.6 nmol min-1 mg-1 protein). Stimulation was significantly higher in HP cells (26 +/- 4%) than in NP cells (7 +/- 4%) (P less than 0.001). The amino acids did not stimulate ouabain-insensitive respiration. The results indicate that an HP diet to weanling rats will increase proximal tubule cell Na, K-ATPase-dependent respiration by enhancing Na entry via the Na-amino acid symports.

Amino Acids↗
PubMed1990

Renal hypertension following aortic constriction is abolished by angiotensin II converting enzyme inhibitor, but not by low-salt diet.

This study evaluates the role of different sodium intakes and the role of angiotensin II in the development and the maintenance of renovascular hypertension in rats with constriction of the aorta proximal to the renal arteries. The rats were studied 3 weeks after surgery when the hypertension was well established. Glomerular filtration rate was decreased and filtration fraction was increased in rats with proximal aortic constriction. Low and high salt intakes had no effect on glomerular filtration and filtration fraction. Treatment with angiotensin II converting enzyme inhibitor increased the glomerular filtration rate and reduced the filtration fraction in rats with proximal aortic constriction to the same levels as in control rats. Serum levels of angiotensin II were about the same in rats with proximal aortic constriction as in control rats. Conclusion. The renovascular hypertension in proximal aortic constriction is influenced by locally formed angiotension II but not by alterations in salt intake.

Angiotensin II↗
PubMed1990

Influence of Na+ intake on dopamine-induced inhibition of renal cortical Na(+)-K(+)-ATPase.

The enzyme L-amino acid decarboxylase (L-AADC), found in abundance in rat proximal tubule cell cytosol, converts L-dopa to dopamine. Dopamine, in turn, suppresses proximal tubule sodium transport by inhibiting Na(+)-K(+)-ATPase activity. We sought to determine whether changes in dietary sodium intake in rats lead to adaptation of dopamine formation and dopamine-induced Na(+)-K(+)-ATPase inhibition. In rats on a high-salt (HS) diet, the maximal velocity (Vmax) of renal cortical L-AADC was 78 +/- 19% higher than that in rats on a low-salt (LS) diet. The Michaelis constant (Km) of the enzyme remained unchanged. In renal cortical tubule cell suspensions the L-dopa-induced inhibition of ouabain-sensitive oxygen consumption (QO2) was significantly greater in rats on HS diet than in rats on LS diet. Furthermore, L-dopa completely inhibited the nystatin-induced rise in QO2 in the HS but not in the LS group. Carbidopa, an inhibitor of L-AADC, abolished the L-dopa-induced inhibition of nystatin-stimulated QO2 in cells from HS rats and was without significant effect in cells from LS rats. L-Dopa-stimulated K+ efflux was greater in cells from HS rats at 28 +/- 1 nmol.min-1.mg protein-1, compared with 7 +/- 6 nmol.min-1.ng protein-1 in cells from LS rats. By contrast, ouabain-stimulated K+ efflux did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Proliferation and intracellular pH in cultured proximal tubular cells.

Renal proximal tubule (PT) cells from adult rats will maintain much of their functional characteristics in short-term primary culture [S. Larsson, A. Aperia, and C. Lechene. Am. J. Physiol. 251 (Cell Physiol. 20): C455-C464, 1986]. This study examines the growth regulation of these highly differentiated cells with particular reference to cell density, intracellular pH (pHi), and the expression of the Na(+)-H+ exchanger. PT cells were obtained from young adult rats and studied after 48 h in culture. The mitotic rate was determined as the labeling index (LI) after [3H]thymidine autoradiography, and pHi was determined by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein quantitative fluorescence microscopy in single cells. Cells were grown either continuously in serum (S) or were serum deprived after 24 h (D). The cells were nonconfluent and grew in colonies. We defined the two peripheral layers of cells in a colony as peripheral (P) cells and the remaining cells as central (C). In C cells LI/h and pHi were in the range of what has been observed under in vivo conditions. In S condition LI/h was 2.2 +/- 0.3% and in D condition was 0.3 +/- 0.1%. LI was significantly higher in P than in C cells both under S (2.5 +/- 0.4-fold) and D conditions (5.6 +/- 0.8-fold). The rapidly growing P cells had a significantly lower pHi than the growth-retarded C cells both under S (7.25 +/- 0.02 vs. 7.30 +/- 0.01, P less than 0.05) and D conditions (7.21 +/- 0.02 vs. 7.28 +/- 0.01, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Inhibition of proximal tubule Na(+)-K(+)-ATPase activity requires simultaneous activation of DA1 and DA2 receptors.

This study examines the receptor mechanisms by which dopamine (DA) inhibits Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in single permeabilized proximal tubule (PCT). Na(+)-K(+)-ATPase activity was inhibited in the presence of both DA1- and DA2-specific agonists but not by either agonist alone. The inhibition induced by DA (10(-6) M) was attenuated in the presence of either of the two DA2-specific antagonists S-sulpiride and YM 09151 at 10(-5) M and in the presence of the DA1 antagonist SCH 23390 (10(-5) M). PCT adenosine 3',5'-cyclic monophosphate (cAMP) levels were significantly increased in the presence of DA and DA1 agonist, but DA2 agonist had no effect on cell cAMP levels. Na(+)-K(+)-ATPase activity was significantly inhibited in PCT incubated with DA2 agonist (10(-5) M) and dibutyryl (DB)-cAMP (10(-6) M) but not with DA2 agonist (10(-5) M) only. PCT Na(+)-K(+)-ATPase activity was also significantly inhibited in the presence of both DA2 agonist (10(-5) M) and forskolin (10(-6) M). Neither DBcAMP (10(-6) M) nor forskolin (10(-6) M) alone inhibited Na(+)-K(+)-ATPase activity. In tubules incubated with DA (10(-8) to 10(-9) M), the presence of DBcAMP (10(-6) M) enhanced the sensitivity by which DA inhibited Na(+)-K(+)-ATPase activity. We conclude that PCT Na(+)-K(+)-ATPase activity is inhibited by a synergistic action of the DA1 and DA2 receptors, with the DA1 receptor acting to increase cell cAMP levels.

Animals↗
PubMed1989

Glomerular adaptation in uninephrectomized young rats.

To study the glomerular adaptation during compensatory renal growth starting in infancy, we assessed afferent effective ultrafiltration pressure (PUF), glomerular filtration area and hydraulic conductivity in rats uninephrectomized (Nx) or sham-operated (S) at 5 days of age. Rats were fed a normal protein diet and studied at 20 and 60 days of age. Single nephron glomerular filtration rate was significantly higher in Nx than in S rats both at 20 days of age (mean +/- SEM: 15.0 +/- 1.5 vs 7.4 +/- 0.7 nl/min) and 60 days of age (80.7 +/- 4.6 vs 43.5 +/- 3.2 nl/min). Afferent effective PUF, estimated by the stop-flow method, was significantly higher in Nx than in S rats both at 20 days (22.5 +/- 0.8 vs 18.3 +/- 0.4 mmHg) and 60 days (28.3 +/- 1.0 vs 23.2 +/- 1.1 mmHg). The filtering area per glomerulus, calculated as the area of the glomerular basement membrane facing both the endothelial and the epithelial cells, but not the mesangial cells, was not different in Nx and in S rats at 20 days (3.0 +/- 0.3 vs 2.8 +/- 0.1 10(4) microns 2), but it was significantly greater in Nx than in S rats at 60 days (23.3 +/- 3.7 vs 9.9 +/- 0.9 10(4) microns 2). The hydraulic conductivity determined in isolated glomeruli was similar in Nx and in S rats at 20 days of age (1.40 +/- 0.11 vs 1.69 +/- 0.23 microliters/min.mmHg.cm2) but was significantly decreased in 60-day-old Nx rats, compared with S rats of the same age (1.52 +/- 0.11 vs 2.35 +/- 0.17 microliters/min.mmHg.cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1989

Studies of terminal differentiation of electrolyte transport in the renal proximal tubule using short-term primary cultures.

There are several lines of indirect evidence suggesting that the renal tubule cells have not yet reached terminal differentiation at birth. Methods used in cell biology can now be applied to study renal ontogeny. This review describes how primary cultures of proximal tubule cells from rats can be used to investigate developmental changes in Na permeability and Na-K-ATPase-mediated transport.

Animals↗
PubMed1989

Ascending pyelonephritis in young rats retards kidney growth.

Several radiological studies have suggested that pyelonephritis in infancy and childhood may result in kidney growth retardation without renal scarring. In the present study, we induced ascending pyelonephritis in 20-day-old rats with intravesical infusion of E. coli. Four days after infusion, E. coli was cultured from all renal cortex. The rats were either left untreated (PNu) or were treated with trimethoprim-sulfa (PNt). The rats were investigated one month after infection and compared with an age-matched control group (C). Seventy-nine percent of the PNu rats had recovered spontaneously from infection. Body weight was the same in all groups. In PNu rats, kidney weight (KW), kidney area (KA) and glomerular filtration rate (GFR) were significantly decreased. KW, KA and GFR were similar in PNt and C rats. The numbers of filtering nephrons were not reduced by the infection. The total cortical DNA content (index of cell number) was significantly lower in PNu (5.30 +/- 0.32 mg) and PNt (6.62 +/- 0.44 mg) than in C rats (8.48 +/- 0.49 mg). The cortical DNA content was significantly lower in PNu than in PNt rats. The cortical protein/DNA ratio was significantly higher in PNu rats than in C rats. The protein/DNA ratio was similar in PNt and PNu rats. The increase in protein/DNA ratio was interpreted as a sign of cell hypertrophy. The inflammatory process as such did not increase the protein/DNA ratio. The kidneys were also examined for structural lesions. Signs of scarring, inflammation and cell necrosis were almost absent in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells.

The cellular localization of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of Mr 32,000 that appears to mediate certain actions of dopamine in the mammalian brain by acting as an inhibitor of protein phosphatase 1, was studied in the kidney of several species. DARPP-32 mRNA and DARPP-32-like immunoreactivity were found in the cytoplasm of cells in the thick ascending limb of the loop of Henle. The specific dopamine DA1 agonist SKF 82526 caused a dose-dependent inhibition of Na+,K+-ATPase activity, which could be blocked by SCH 23390, a specific DA1 antagonist, and by PKI-(5-24) amide, a specific inhibitor of cAMP-dependent protein kinase. The results indicate that DA1 dopamine receptors and DARPP-32, an intracellular third messenger for dopamine, are part of the signal-transduction process for dopamine acting on renal tubule cells.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Na,K-ATPase activity in renal tubule cells from Milan hypertensive rats.

Several abnormalities of cation transport have been described in the Milan hypertensive rats (MHS). In this study we examined Na,K-ATPase activity in proximal convoluted tubules (PCT) cells and medullary thick ascending limb of Henle cells (TAL) from MHS and from the Milan normotensive rats (MNS). Na,K-ATPase activity was determined as 32P-ATP hydrolysis in single tubule segments. Na,K-ATPase activity (pmol Pi/mm t/h) was significantly higher in MHS than MNS both in PCT (903 +/- 227 n = 8 v 506 +/- 285 n = 12) and TAL (4324 +/- 800 n = 5 v 3063 +/- 625 n = 5). Na,K-ATPase dependent respiration was determined in PCT cell from MNS and MHS. Under basal condition Na,K-ATPase dependent respiration (mumol O2/mg protein/h) was higher in MHS than in MNS (24.2 +/- 1.8 n = 5 v 16.1 +/- 0.4 n = 5). When the cells were Na loaded by amphotericin Na,K-ATPase dependent respiration increased significantly more in MHS than MNS (38.4 +/- 1.6 v 26.8 +/- 2.2 n = 4). Thus, Na,K-ATPase activity is higher in renal tubule cells both at normal intracellular Na and after the cells have been Na loaded. The results indicate that regulation of Na homeostasis in renal tubule cell is different in MHS and MNS.

Amphotericin B↗