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Biomedical subjects

S Klahr

Publications and source records attributed to S Klahr.

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

Eicosanoid production by isolated glomeruli of rats with unilateral ureteral obstruction.

The production of PGE2 6-keto PGF1 alpha and TxB2 under basal conditions and after exposure to angiotensin II was examined in vitro in isolated glomeruli from sham-operated control rats and rats with unilateral ureteral obstruction of 24 hour duration, that were or were not pretreated with an inhibitor of the angiotensin I converting enzyme (ACE). Basal prostanoid production was greater in glomeruli from the obstructed kidney (OK) than in glomeruli from the contralateral kidney (CLK) of rats with obstruction or glomeruli from the kidneys of sham-operated rats. Glomeruli obtained from the CLK of rats with unilateral obstruction also produced more PGE2 and 6-keto PGF1 alpha than glomeruli obtained from kidneys of sham-operated rats. Administration of an ACE inhibitor to rats with unilateral obstruction in vivo returned basal prostanoid production in vitro to levels seen in glomeruli of sham-operated rats. The increase in prostanoid production in response to angiotensin II added in vitro was less in glomeruli from rats with unilateral obstruction than in glomeruli from sham-operated rats. However, the response was restored to that seen in glomeruli of sham-operated rats after blockade of angiotensin II synthesis in vivo in rats with unilateral obstruction. Blockade of angiotensin II synthesis in sham-operated rats did not affect prostanoid synthesis by their glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Effects of probucol on renal function in rats with bilateral ureteral obstruction.

To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.

Animals↗
PubMed1990

Role of ANG II in eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction.

The production of prostaglandin (PG) E2, 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) under basal conditions and after exposure to angiotensin II (ANG II) or arginine vasopressin (AVP) was examined in vitro in isolated glomeruli. The glomeruli were obtained from control rats and rats with bilateral ureteral obstruction (BUO) of 24-h duration that were pretreated or not with an inhibitor of the angiotensin I converting enzyme (ACE). Basal prostanoid production was greater in isolated glomeruli from BUO rats than in controls. Administration of an ACE inhibitor, enalaprilat, given in vivo returned basal prostanoid production by isolated glomeruli of BUO rats to levels seen in glomeruli of control rats. The prostanoid production in response to addition of ANG II or AVP in vitro was blunted in glomeruli from BUO rats, but the response was restored to "normal" after blockade of ANG II synthesis in vivo in BUO rats. Blockade of ANG II synthesis in vivo did not affect prostanoid synthesis by isolated glomeruli of control rats. The prostanoid generation in response to addition of both ANG II and arachidonic acid in vitro compared with ANG II addition alone was not significantly stimulated in glomeruli from BUO rats. In contrast, it was significantly stimulated in glomeruli of control rats. The results indicate that endogenous ANG II has an important role in the increased synthesis of prostanoids found in isolated glomeruli of rats with BUO and that the in vitro prostanoid production in response to ANG II and AVP can be restored to normal when the synthesis of ANG II is inhibited in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Bladder contributes to eicosanoids excreted in urine.

The excretion of eicosanoids was examined in urine collected from the bladder or the ureter in normal rats. We found that the excretion of thromboxane B2 (the stable metabolite of thromboxane A2), prostaglandin E2, and 6-ketoprostaglandin F1 alpha was significantly greater in urine collected from the bladder than in urine collected from the ureter. This suggests that the bladder contributes significantly to the amount of eicosanoids present in the urine.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin.

The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function.

Acute Disease↗
PubMed1990

A high cholesterol diet ameliorates renal tubular lesions in diabetic rats.

These studies examine the effect of cholesterol feeding in normal rats and in rats with streptozotocin-induced diabetes mellitus. Four groups were studied: normal rats fed either a standard rat chow or a standard rat chow supplemented with cholesterol and diabetic rats fed standard chow or standard chow plus cholesterol. Diabetic rats fed a standard diet excreted more creatinine and urea in the urine, had higher levels of blood urea nitrogen, and lower serum albumin levels than rats fed standard diet plus cholesterol. Blood glucose levels were similar in the two groups; however, diabetic rats given cholesterol had a greater body weight at the end of the study than diabetic rats eating standard chow. Urine volumes and sodium and potassium excretion in the urine were greater in diabetic rats fed a standard diet than in those fed a high cholesterol diet. Diabetic rats fed a standard diet had distinctive renal lesions characterized by swelling of tubular epithelial cells with clearing of cytoplasm. The nephron segments involved by this striking vacuolar change were the distal convoluted tubule and the thick limbs of Henle's loop. These lesions were identical to those described by Armanni-Ebstein in severely glycosuric patients. These lesions were not observed in any of the animals of the other three groups (including diabetic rats fed a high cholesterol diet). Glomeruli were normal in animals of all groups. Thus, cholesterol administration prevents the development of the Armanni-Ebstein lesions in diabetic rats despite persistent hyperglycemia. The mechanism by which cholesterol administration prevents the accumulation of glycogen in distal tubule cells has not been elucidated. It is suggested that glycogen accumulation in distal tubular segments may explain the greater urine volumes, natriuresis, kaliuresis, and proteinuria observed in diabetic animals fed a standard diet when compared with rats fed the same diet plus cholesterol.

Animals↗
PubMed1990

Renal cortical release of a specific macrophage chemoattractant in response to ureteral obstruction.

Acute ureteral obstruction results in a large influx of macrophages into the cortex and medulla of the obstructed kidney. We examined supernatants from short-term cultures of acutely obstructed and contralateral control renal cortices to determine whether differential production of a chemoattractant for macrophages could account for the cellular infiltrate observed in the obstructed kidney. Using a microchemotaxis assay, supernatants from obstructed renal cortex did demonstrate significantly more chemotactic activity for rat peritoneal macrophages than did supernatants from the contralateral kidneys. This activity showed a dose-response relationship with macrophage migration, peaked between 4 and 12 hours of obstruction, and declined with longer periods of obstruction. The activity was heat stable. It was retained by an octadecylsilane column, and eluted with methanol. Partitioning of the methanol fraction into aqueous and organic phases demonstrated significant activity in the organic phase. In summary, the acutely obstructed rat kidney releases a previously undescribed chemotactic factor that behaves as a lipid. This factor may account for the mononuclear cell infiltrate observed during obstruction.

Animals↗
PubMed1989

Eicosanoids: role in experimental renal disease.

Because of their vasodilator and vasoconstrictor properties, vasoactive prostaglandins and thromboxane A2 have been proposed as modulators of the hemodynamic changes that occur in experimental models of renal disease. Increased synthesis of vasodilatory prostaglandins (PGE2) and perhaps prostaglandin I2 (PGI2) play a role in the maintenance of renal blood flow and GFR during states of impaired perfusion. In contrast, thromboxane A2 has been implicated as the vasoconstrictor responsible for the reduction of renal blood flow and GFR in certain animal models of experimental renal disease. These products and other metabolites of arachidonic acid may also participate in the immunological events underlying the onset and/or progression of experimental renal disease. It is evident that the pathophysiologic role of eicosanoids in experimental renal disease is not fully understood. Additional studies and further understanding of the many other potential roles of eicosanoids on immunological events, hemodynamic states, mesangial cell physiology, etc. are needed to comprehend more fully the extent of the participation of eicosanoids in the pathogenesis and pathophysiology of renal disease.

Animals↗
PubMed1989

The effects of atrial peptide in humans with chronic renal failure.

The role of atrial peptide in humans with chronic renal insufficiency is uncertain. Therefore, the effects of synthetic atrial peptide (atriopeptin III, 24 amino acids) infusion on renal function and solute excretion were examined in 16 subjects with chronic renal insufficiency of diverse etiologies. After a two-hour baseline period, atrial peptide was infused for four hours in doses ranging from 0.005 to 0.1 micrograms/kg/min. When all doses were combined, absolute and fractional excretions of sodium increased significantly from baseline values (130 +/- 15 to 231 +/- 28 microEq/min and 3.57 +/- 0.57 to 6.03 +/- 1.26%, respectively, P less than 0.05). Significant increases in urinary excretion of chloride, calcium, and phosphorus were also seen during atrial peptide infusion. Increased absolute and fractional phosphorus excretion persisted during the two-hour postinfusion period, while excretion of other solutes returned to baseline. Glomerular filtration rate (GFR) increased by greater than 20% in five of 16 subjects. Two subjects with severe renal insufficiency (GFR = 9 and 12 mL/min) had no apparent response to atrial peptide infusion. Subjects receiving doses of 0.05 and 0.1 microgram/kg/min had significant falls of mean arterial pressure by the last hour of infusion. A dose-dependent effect of atrial peptide on sodium excretion was suggested, but not statistically significant. No apparent dose-dependent effect was seen on GFR or other solute excretions. Despite the presence of chronic renal insufficiency, atrial peptide increased renal solute excretion in most subjects. The demonstration that atrial peptide retains its diuretic and natriuretic effect in the presence of renal insufficiency supports the hypothesis that atrial peptide plays an important adaptive role in sodium homeostasis of the failing kidney.

Adult↗
PubMed1989

Prior inhibition of vasoconstrictors normalizes GFR in postobstructed kidneys.

The present studies were designed to analyze the potential contribution of angiotensin II and thromboxane A2 to the remarkable decrease in glomerular filtration rate (GFR) and renal plasma flow observed after unilateral release of 24-hour bilateral ureteral obstruction. Pretreatment of the animals with inhibitors of either thromboxane or angiotensin synthesis for 48 hours prior to and during obstruction eliminated the contribution of these vasoconstrictors. Inhibition of these vasoconstrictors during the period of obstruction results in a greater increase in renal plasma flow and GFR than when inhibition was accomplished after release of the obstruction. These data suggest a greater role for these vasoconstrictors in the decrease in GFR that occurs with obstruction. Simultaneous inhibition of thromboxane and angiotensin production normalized GFR of the postobstructed kidney. Administration of atrial peptide after release of obstruction in the different groups of rats resulted in further increases in GFR, urine flow and absolute sodium excretion. It is suggested that atrial peptide participates in the renal hemodynamic changes that occur in the postobstructed kidney.

Acrylates↗
PubMed1989

Increased sodium transport by cortical collecting tubules from remnant kidneys.

To determine whether intrinsic changes in cortical collecting tubule (CCT) transport contribute to the maintenance of sodium and acid-base balance after loss of renal mass, we studied transport functions in isolated perfused CCT from rabbit remnant kidneys. The rabbits were sacrificed three weeks after surgical reduction of renal mass (by 3/4 to 7/8) at which time they were mildly azotemic but had no systemic electrolyte or acid-base disturbances. When perfused by standard methods in vitro, CCT from remnant kidneys exhibited sodium transport rates (lumen-to-bath 22Na-flux) approximately twice as high as those in CCT from control animals (111 +/- 19 vs. 54 +/- 7 pmol/min mm, P less than 0.02). A similar difference was present in the ouabain-sensitive sodium fluxes (81 +/- 16 vs. 39 +/- 8 pmol/min mm, P less than 0.05). In contrast, there were no significant differences in net bicarbonate transport. Significant hypertrophy of the remnant kidney CCT was reflected by 30 to 45% increases in tubule diameters. To examine the possible role of differences in food intake, we studied a separate group of weight-matched, pair-fed sham-operated and remnant kidney rabbits. Similar differences in total and ouabain-sensitive 22Na-flux, and in tubule size persisted in the pair-fed animals. A dissociation between active sodium transport and tubule hypertrophy was documented in the outer medullary collecting tubule: despite the lack of active sodium transport, hypertrophy was present. Our studies show that loss of renal mass results in a selective augmentation of certain transport processes in the CCT, implying selective or specific signals and mechanisms.

Adaptation, Physiological↗
PubMed1989

Effect of leukocyte depletion on the function of the postobstructed kidney in the rat.

We have observed an influx of leukocytes, predominantly macrophages, into the cortex and medulla of the kidney following ureteral obstruction. To examine the potential contribution of these infiltrating cells to the decrease in GFR and RPF that occurs following ureteral obstruction, 16 male Lewis rats (wt 246.4 +/- 4.0 g) were studied in the awake state three hours after unilateral release of 24 hours of bilateral ureteral obstruction (BUO). Eight rats were not irradiated, and eight rats received 1315 rads one day prior to the obstruction. The leukocyte infiltrate following 24 hours of ureteral obstruction was quantified with and without prior irradiation in an additional eight rats. Irradiation reduced cortical infiltration (27.05 +/- 3.07 x 10(5) vs. 1.2 +/- 0.83 x 10(5) cells/g tissue) and medullary infiltration (13.6 +/- 1.79 x 10(5) vs. 0.86 +/- 0.45 x 10(5) cells/g tissue) of leukocytes following BUO (P less than 0.001 for both) and increased postobstruction GFR (1.58 +/- 0.12 vs. 2.97 +/- 0.15 ml/min/kg body wt, P less than 0.001). Eleven rats, six of which received irradiation, underwent sham laparotomy without BUO in order to assess the effect of irradiation alone on renal function. Irradiation had no effect on the renal function of non-obstructed rats. Urinary excretion of thromboxane B2 increased following BUO and this rise was significantly blunted by irradiation prior to BUO (9.53 +/- 2.14 vs. 32.46 +/- 4.95 vs. 19.03 +/- 1.94 pg/min). Fractional excretion of sodium and water was reduced by irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗