Biomedical subjects

E Podjarny

Publications and source records attributed to E Podjarny.

At least 19 recordsLinked to original sources

PubMed1992

Effect of sodium and chloride depletion on urinary prostaglandin F2 alpha excretion in potassium loaded rats.

Previous studies have shown that the urinary excretion of prostaglandin (PG) F2 alpha is stimulated by potassium (K) loading. Because changes of sodium chloride (NaCl) intake also affect renal PG production, in this study we investigated the interaction between the effect of K and that of concomitant reduction of Na and Cl intake. The urinary excretion of PGF2 alpha and PGE2 was measured in 12 groups of female rats on normal, high or low K intake. Na and Cl intake were adjusted so that rats had normal intake (controls, C), were selectively Cl depleted (CD), selectively Na depleted (ND) or Na and Cl depleted (NCD). In rats with normal K intake, urinary PGF2 alpha was not modified by changes of Na or Cl intake, whereas PGE2 was increased in by Cl depletion (in both NCD or CD groups). Potassium chloride loading increased urinary PGF2 alpha and selective Na depletion (ND group) induced a further increase. On the other hand, PGF2 alpha was not stimulated when K load was associated with Cl depletion. Urine PGF2 alpha was directly correlated with plasma aldosterone and urinary kallikrein. Urinary PGE2 did not change with K-loading. The results suggest that PGF2 alpha participates in the renal adaptation to KCl-loading but not when K is accompanied by non-Cl anions.

Aldosterone↗

PubMed1992

Altered prostaglandin synthesis and impaired sodium conservation in the kidneys of old rats.

1. The aim of this investigation was to study the role of prostaglandins in the impaired Na+ conservation of the ageing kidney. 2. We measured the urinary excretion of thromboxane B2, 6-keto-prostaglandin F1 alpha and prostaglandin E2 in young (3-4 months) and old (20-21 months) rats after 12, 24 and 36 h of Na+ deprivation. In a separate protocol, we measured prostanoid synthesis by isolated glomeruli, cortical homogenates, medullary slices and papillary slices from young and old rats in basal conditions and after 15 days of dietary Na+ deprivation. 3. In the acute study, urinary excretion of 6-keto-prostaglandin F1 alpha and prostaglandin E2 decreased in young but not in old rats. Urinary excretion of prostaglandin E2 was lower in old rats, but did not vary significantly with Na+ deprivation. 4. In old rats, thromboxane B2 synthesis was increased in all the portions of the kidney except the medulla. Production of 6-keto-prostaglandin F1 alpha was elevated in glomeruli and tended to increase in the cortex. Prostaglandin E2 synthesis was also elevated in the cortex. Thromboxane B2 synthesis tended to increase in the medulla and was enhanced in the papilla. After Na+ deprivation, only glomerular prostaglandin E2 synthesis increased in young rats. In old rats, cortical and papillary synthesis of 6-keto-prostaglandin F1 alpha increased, whereas prostaglandin E2 synthesis did not change. 5. The results suggest increased thromboxane synthesis in the ageing kidney. Increased prostacyclin and prostaglandin E2 synthesis may be an attempt to counteract enhanced thromboxane production.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Adriamycin nephropathy: a model to study effects of pregnancy on renal disease in rats.

The influence of pregnancy on the evolution of primary renal disease is still a matter of controversy. Hypertension and derangement of renal function may occur. The pathophysiology of these complications is poorly understood. In the present study, we assessed the influence of pregnancy on the evolution of adriamycin (Adr) nephropathy. Four groups of animals were studied: 1) control virgin rats (C), 2) normal pregnant rats (NP), 3) virgin rats with nephropathy (Adr), and 4) pregnant rats with nephropathy (Adr-P). Inulin clearance measured at the end of pregnancy in awake rats was similar in NP (1.68 +/- 0.20 ml/min) and C (1.39 +/- 0.03 ml/min). In Adr-P rats, it tended to decrease (1.22 +/- 0.7 vs. 1.93 +/- 0.44 ml/min in Adr rats). Mean arterial pressure was increased in Adr-P rats (137 +/- 2.5 vs. 95 +/- 3.2 mmHg in NP; P < 0.001). Urinary protein excretion was 216 +/- 61 mg/day in Adr-P compared with 28.7 +/- 18 mg/day in Adr (P < 0.001). A significant increase in the glomerular thromboxane B2-to-prostaglandin E2 ratio was found in Adr-P rats (1.15 +/- 0.26 vs. 0.52 +/- 0.12 in Adr rats; P < 0.03). In NP rats, no change was observed. Kidneys and placentas were normal on light and electron microscopy. Thus pregnant rats with adriamycin nephropathy developed a clinical picture with several features of preeclampsia. Changes in glomerular prostanoid synthesis might play a role in the development of this complication.

Anesthesia↗

PubMed1992

Stimulation of renal prostanoid synthesis by potassium loading in the rat.

In vitro we measured the urinary excretion and synthesis of prostaglandins (PGE2, 6-keto-PGF1 alpha, thromboxane B2 and PGF2 alpha) by isolated glomeruli, cortical homogenates, medulla and papilla in KCl-loaded rats (KCl+, average K intake: 17 mmol/day for 20 days) and in rats loaded with non-Cl K salts (KCl-, average K intake: 21 mmol/day) as compared with control rats. In 2 separate groups of rats (KCl+ and KCl-) the urinary excretion of prostaglandins was measured after variations of K intake from an average of 4 to 20 mmol/day in 5-day periods. Glomerular PGE2 synthesis tended to decrease in KCl+, whereas it increased in KCl- rats. 6-Keto-PGF1 alpha and TXB2 did not vary, and PGF2 alpha decreased in both K-loaded groups. In the cortex, KCl loading decreased PGE2 synthesis. In KCl-, cortical TXB2 decreased. In the medulla, KCl loading increased the synthesis of TXB2 and PGF2 alpha, but not that of PGE2 and 6-keto-PGF1 alpha. In KCl- rats, TXB2 but not PGF2 alpha increased and PGE2 synthesis was also elevated. In the papilla, TXB2 synthesis increased in both KCl+ and KCl- rats. The urinary excretion of 6-keto-PGF1 alpha and TXB2 increased in both KCl+ and KCl- rats, whereas PGF2 alpha increased only in KCl+ rats. The changes of glomerular prostaglandin synthesis during K loading could dilate the glomerular vasculature, in keeping with the known vasoactive effects of the cation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1991

Effect of the prostacyclin analogue iloprost in sodium-depleted rats pretreated with captopril.

Previous studies have shown that administration of captopril to sodium-depleted rats decreases the glomerular filtration rate (GFR) and blunts the increase in glomerular prostacyclin synthesis normally occurring in response to sodium depletion. To clarify the relationship between these two responses, iloprost, a stable analogue of prostacyclin, was administered to Na-depleted, captopril-treated (LNC) rats. At a dosage not affecting systemic blood pressure (12.5 ng/kg/min), iloprost increased GFR in LNC rats by 25% (from 0.26 +/- 0.03 to 0.35 +/- 0.03 ml/min/100 g body wt, P less than 0.01), without significant effects on renal plasma flow. No effect was observed in control rats. The results suggest that altered prostacyclin synthesis could contribute to the decrease of GFR in this model.

Animals↗

PubMed1990

Hypercalcemic nephropathy: chronic disease with predominant medullary inner stripe injury.

Because of the recently observed augmentation of medullary hypoxic injury by calcium in isolated perfused rat kidneys (Kidney Int 34:186-194, 1988), renal morphology of chronic, prolonged hypercalcemia was investigated in vivo. Rats were treated with repeated injections of vitamin D2 (400,000 units/week) for two to eight weeks. Chronic elevation of plasma calcium from 2.1 to 2.8 mmol/liter (P less than 0.001) was associated by a fall in maximal urine osmolality with no change in glomerular filtration rate. The most significant morphological alterations occurred in the inner stripe of the outer medulla; these changes were characterized by a sequence of active injury with subsequent destruction and atrophy of the medullary thick ascending limbs, fibroblastic and lymphocytic infiltration, and secondary dilatation of collecting ducts. Similar changes occurred in the medullary rays. These alterations were accompanied by increased renal prostanoid production and a predisposition to acute kidney failure from indomethacin. Because of its selective occurrence in zones of poorest oxygen supply, this inner stripe injury may derive from vulnerability to hypoxia and may play a role in some chronic nephropathies.

Animals↗

PubMed1990

NaCl modulates captopril effects on glomerular prostaglandin synthesis and glomerular filtration.

Captopril stimulates glomerular prostaglandin (PG) synthesis and increases glomerular filtration rate (GFR) in Na-repleted rats, whereas, in Na-depleted rats, it fails to stimulate PG synthesis and decreases GFR. In the present work the influence of chronic and acute NaCl loading on PG synthesis and renal function was studied in Na-depleted rats receiving captopril (LNC rats). Glomerular PGE2 and 6-keto-PGF1 alpha were not increased in LNC rats and were significantly lower than in Na-depleted rats (LN). Na repletion, while continuing captopril, increased PG synthesis above control levels. Addition of captopril in vitro to the incubation medium stimulated PGE2 synthesis in glomeruli of control rats, whereas it depressed it in LN rats. Acute loading with NaCl in LNC rats increased inulin and PAH clearances to values significantly greater than in control rats and similar to those of normal rats receiving captopril. Comparable volume loading with isotonic mannitol or 3% albumin increased inulin and PAH clearances only to control values. The specific effect of NaCl in acute loading was prevented by cyclooxygenase inhibition and was not mediated by increased systemic blood pressure. The results provide evidence that the effects of captopril on glomerular PG synthesis and renal function depend on the state of Na balance.

Animals↗

PubMed1990

Potassium load prevents the decrease of GFR induced by captopril in sodium-depleted rats.

Captopril decreases the glomerular filtration rate (GFR) in Na-depleted rats and inhibits the stimulation of glomerular prostanoid synthesis induced by Na depletion. Because K loading stimulates glomerular prostanoid production in normal rats, we studied the effects of K loading in Na-depleted captopril-treated (LNC) rats. Potassium, but not Cl, loading stimulated the glomerular synthesis of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and thromboxane B2 (TxB2). Urinary kallikrein-like activity (UKALLV) and plasma aldosterone increased in K-loaded animals. LNC rats had lower clearances of inulin (CIN) and p-aminohippurate (CPAH) than controls (0.22 +/- 0.02 vs. 0.94 +/- 0.07 and 0.56 +/- 0.12 vs. 2.23 +/- 0.23 ml.min-1.100 g body wt-1, both P less than 0.01). KCl-loaded LNC rats had CIN and CPAH greater than LNC (0.64 +/- 0.16 and 1.90 +/- 0.28 ml.min-1.100 g body wt-1, P less than 0.01). Similar results were observed in LNC rats loaded with a K solution not containing Cl, but not in LNC rats loaded with a mixture of CaCl2, MgCl2, and HCl. In KCl-loaded LNC rats, cyclooxygenase inhibition decreased CIN from 0.49 +/- 0.09 to 0.30 +/- 0.08 ml.min-1.100 g body wt-1 (P less than 0.01). Aprotinin did not affect renal function despite significant decrease of UKALLV. We conclude that K loading prevents the decrease of GFR induced by captopril in Na-depleted rats and that this might be mediated by stimulation of glomerular prostanoid synthesis.

Aldosterone↗

PubMed1990

Captopril, but not diltiazem, favorably affects the course of early chronic renal disease in rats.

The concepts that increased intracellular Ca2+ content and increased glomerular capillary pressure play an important role in the progression of chronic renal diseases has led to the suggestion that treatment with calcium-blocking agents (diltiazem; CBB) or converting enzyme inhibitors (captopril; CEI) may be indicated to prevent renal failure. We studied the effects of CCB and CEI on the early course of adriamycin (ADR) nephropathy, where glomerular pressure has been shown to be unchanged, blood pressure was only mildly elevated and renal failure incipient. Animals were studied 2, 7, 12, 16 and 20 weeks after the second injection of ADR, 2 mg/kg. In treated rats, blood pressure remained normal. At the end of the study, proteinuria and serum creatine were lower in ADR-CEI than in ADR rats (149 +/- 42 vs. 616 +/- 90 mg/day, p less than 0.01 and 0.36 +/- 0.04 vs. 0.58 +/- 0.02 mg%, p less than 0.01, respectively). ADR-CCB had values similar to those of untreated ADR rats. Mesangial expansion and focal glomerulosclerosis were present only in ADR and ADR-CCB rats, whereas in ADR-CEI rats the glomeruli were virtually normal. Glomerular 45Ca uptake was increased in ADR, decreased in ADR-CCB rats, and normal in ADR-CEI. Glomerular 6-keto PGF1 alpha and TxB2 were significantly increased in ADR rats, and both treatments decreased TxB2. The results suggest that endogenous angiotensin II is important for the early progression of glomerular injury toward renal insufficiency, while tissue Ca2+ accumulation may play an important role in more advanced phases.

Animals↗

PubMed1990

Effects of changes in sodium balance on prostaglandin synthesis and prostaglandin E2 9-ketoreductase activity in the rat kidney.

The in vitro synthesis of prostaglandins E2 and F2 alpha by renal cortex, medulla and papilla was measured in normal rats and in rats receiving either a low or a high sodium intake for 14 days. The production of both prostaglandins was unchanged in the cortex. In the medulla, both low and high sodium intakes led to a similar decrease in prostaglandin E2 synthesis in vitro, but prostaglandin F2 alpha synthesis was unchanged. In the papilla, a low sodium intake increased prostaglandin E2 synthesis. The activity of prostaglandin E2 9-ketoreductase, a cytosolic enzyme catalysing the conversion of prostaglandin E2 to prostaglandin F2 alpha, was unchanged in cortical preparations. In medullary slices, prostaglandin E2 9-ketoreductase activity was decreased by both sodium depletion and loading. In the papilla, prostaglandin E2 9-ketoreductase activity was slightly decreased by sodium loading and increased with sodium depletion. These results obtained in the rat are at variance with findings in the rabbit. The role played by prostaglandin E2 9-ketoreductase in the regulation of prostaglandin biosynthesis during changes of sodium balance remains controversial.

Animals↗

PubMed1990

Atrial natriuretic peptide-induced increase of glomerular filtration rate, but not of natriuresis, is mediated by prostaglandins in the rat.

This study addressed the question of whether some renal effects of atrial natriuretic peptide (ANP) are mediated by prostaglandins (PGs). Inhibition of PG synthesis (aspirin, 10 mg/kg) abolished the increase in inulin clearance (CIN) induced by ANP in rats. In contrast, diuresis and natriuresis remained significantly elevated after aspirin administration. ANP, either infused in vivo immediately before sacrifice or added to the incubation tubes, stimulated the synthesis of PGE2 and 6-keto-PGE1 alpha by isolated rat glomeruli but not by medullary or papillary slices. We conclude that the effect of ANP on the glomerular filtration rate is PG dependent, whereas that on diuresis and natriuresis is direct.

Animals↗

PubMed1989

Effects of sodium depletion on renal prostanoid synthesis in rats: influence of the converting enzyme inhibitor captopril.

1. The synthesis of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX) B2 by isolated glomeruli, cortical tubules, inner medullary slices and outer medullary slices was measured in salt-depleted (LNa) rats and in salt-depleted rats receiving captopril (LNa-CEI). Animals were studied before and after 4, 9 and 15 days of Na+ depletion. 2. Na+ balance was reached in LNa rats after 4 days. Blood pressure and creatinine clearance remained stable. Serum Na+ decreased from 140 +/- 1 to 126 +/- 1 mmol/l (mean +/- SEM, P less than 0.01). In contrast, LNa-CEI rats were unable to conserve Na+ adequately: fractional excretion of Na+ and natriuresis were constantly greater than in LNa animals. As a consequence, LNa-CEI rats developed severe hyponatraemia, lost weight and their creatinine clearance decreased. 3. The glomerular synthesis of PGE2, PGF2 alpha and 6-keto-PGF1 alpha, but not of TXB2, was significantly increased in LNa rats. In LNa-CEI rats, the synthesis of PGE2 and 6-keto-PGF1 alpha was similar to control values, but PGF2 alpha and TXB2 synthesis was elevated at day 9. In cortical tubules, PGE2 and PGF2 alpha were unaffected by Na+ depletion, but 6-keto-PGF1 alpha and TXB2 were increased and a similar trend was observed in LNa-CEI rats. In outer medulla of LNa rats, a decrease in all the eicosanoids measured was observed at day 4. In LNa-CEI animals, the synthesis of PGE2 and PGF2 alpha, but not of 6-keto-PGF1 alpha and TXB2, was significantly depressed. In inner medulla, Na+ depletion only tended to decrease PGF2 alpha and 6-keto-PGF1 alpha, but in the presence of captopril, the synthesis of all prostanoids was significantly decreased.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Changes in renal prostanoid synthesis induced by potassium loading in rats.

Previous works have demonstrated changes in the urinary excretion of prostaglandins (PG) in response to changes in potassium (K) or sodium (Na) intake. In the present study, the production of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2 (TXB2) by isolated glomeruli, cortical homogenates, medullary and papillary slices was measured in K-loaded rats on either a normal or a low Na intake. In glomeruli, K loading increased selectively PGE2 synthesis. In Na-depleted animals, all prostanoids were elevated and K loading did not induce a further increase. In cortical and medullary preparations, PGE2 was decreased by K loading irrespective of the state of Na balance. In papilla, PGE2 decreased (in all K-loaded rats) and PGF2 alpha increased (only in rats with normal Na intake). 6-Keto-PGF1 alpha and TXB2 did not change significantly. No correlation was present between changes of PG synthesis and urinary kallikrein excretion. The results demonstrate a specific effect of K on PGE2 and PGF2 alpha, and suggest a role for these substances in K homeOstasis.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Thrombin inhibits the synthesis of prostanoids by isolated glomeruli and peritoneal macrophages in rats.

Activation of macrophages and release of mediators that activate the coagulation system characterize proliferative glomerulonephritis. To evaluate the possible role of prostanoids in this process, isolated rat glomeruli (G) and peritoneal macrophages (M) or a combination of the two (G + M) were incubated in the presence of thrombin (2 U/ml). In G, thrombin inhibited only the synthesis of thromboxane B2. In M and G + M incubations, the synthesis of prostaglandin I2 and thromboxane A2 was inhibited by thrombin. This effect was abolished by the addition of arachidonic acid. As prostanoids may play a modulatory role in the interaction between macrophages and glomerular cells, inhibition of their synthesis by thrombin might enhance macrophage activity.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Role of glomerular prostanoid in control of glomerular filtration rate in rats.

It is generally accepted that the main action of glomerular prostanoids (GPs) on glomerular filtration rate (GFR) is to modulate the activity of different vasoconstrictors, specially in states of renal hypoperfusion. However it was also suggested that GPs may directly affect GFR. The present study was focused on this last hypothesis, in different experimental models, in rats. In adriamycin induced acute renal failure, the transient decrease of GFR is associated with higher levels of thromboxane B2. Later on, when GFR returns to normal, vasodilator prostaglandins synthesis was also increased. In captopril induced renal failure in Na depleted rats (where GPs synthesis remained normal), stimulation of PGE2 and PGI2 production by K and NaCl was associated with a significant improvement of GFR. Furthermore, the increase in GFR induced by NaCl was prevented by inhibition of prostaglandin synthesis. Infusion of atrial natriuretic peptide in euvolemic rats induce a marked elevation both of GFR and PGE2 synthesis. It was abolished by previous administration of prostaglandin synthesis inhibitor. In conclusion, glomerular prostanoids may influence GFR, either directly, or as mediator or modulator of other vasoactive hormones.

Acute Kidney Injury↗

PubMed1988

Prostanoids in renal failure induced by converting enzyme inhibition in sodium-depleted rats.

Clearances of inulin (CIn) and p-aminohippurate (CPAH) were measured in four groups of rats before and after intravenous administration of acetylsalicylic acid (ASA): 1) controls, on normal Na intake, 2) captopril-treated (30 mg.kg-1.day-1) on normal Na intake, 3) Na depleted, and 4) Na depleted, captopril-treated. In Na-depleted animals, CIn and CPAH were similar to controls but decreased significantly with ASA. In Na-depleted, captopril-treated rats, CPAH was slightly decreased, but CIn was significantly reduced (P less than 0.01). Both were not affected by ASA. Urine output was unchanged and the kidneys appeared normal on histological examination. The production of prostaglandins E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TxB2) was measured in isolated glomeruli, cortical tubule suspensions, and medullary and papillary slices. Captopril increased PGE2 production by glomeruli and PGF2 alpha and TxB2 synthesis in papillary slices. Na depletion selectively enhanced the production of PGE2 by glomeruli and papillae. In contrast, the synthesis of prostanoids was significantly decreased in captopril-treated, Na-depleted rats. These findings suggest that in this model, functional nonoliguric renal failure may be related to abnormalities of prostanoid synthesis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

Effects of sodium loading on the renal synthesis of prostanoids in the rat.

1. The production of prostaglandin (PG) E2, F2 alpha and thromboxane B2 (TXB2) by isolated glomeruli, cortical tubular suspensions and medullary and papillary slices was measured in normal Long-Evans rats 4, 8 and 14 days after starting on oral Na+ load and the results were compared with those of rats on a normal Na+ intake. 2. In glomeruli, PGE2 decreased at days 4 and 8, and returned to normal at 14 days. PGF2 alpha decreased only at day 4 and TXB2 decreased in all Na+-loaded animals. In cortical suspensions, a transient decrease of PGE2 was observed at day 4. In medullary slices, PGE2 and TXB2 decreased in all experimental periods. In contrast, in papillae, a significant increase of PGE2 was observed with Na+ loading at day 8, but PGF2 alpha and TXB2 did not change consistently. 3. Similar changes were observed in rats with hypothalamic diabetes insipidus (DI rats) Na+ loaded for 4 days, as compared with DI rats on a normal Na+ intake. 4. The results suggest that prostanoids participate in the renal adaptation to an increased Na+ intake, and that this response is relatively independent of the presence of antidiuretic hormone.

Animals↗

PubMed1986

Effect of angiotensin II on prostanoid synthesis in isolated rat glomeruli.

The influence of angiotensin II (ANG II) on the synthesis of glomerular prostanoids is controversial, possibly because of the different methodologies employed. In order to assess this inter-relationship isolated rat glomeruli were incubated with and without shaking. The use of shaking during incubation significantly increased the amounts of prostanoid synthesized, most probably because of continuous non-specific activation of phospholipase (PLA2) activity. After preincubation in a non-shaking bath, ANG II was added for a second incubation period. A marked increase of prostaglandin (PG) E2, and, to lesser degree, of thromboxane (TX) B2 was noted, with no change on PGF2 alpha synthesis. These results show (a) that preincubation without shaking, by lowering the non-specific activation of the PLA2 activity, may unmask, in vitro, specific peptide stimulation, and (b) that ANG II, stimulating principally PGE2 synthesis, may modify the vasoactive status of the glomerular vasculature.

Angiotensin II↗