Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been difficult to produce a good animal model for cyclosporine nephrotoxicity. It has been suggested that by following 20 minutes of renal ischemia with four daily doses of cyclosporine 60 mg/kg intraperitoneally, one can create a model of reproducible renal failure. We observed excessive mortality (65%), due in part to cyclosporine's CNS effects, with these combined insults in the Munich Wistar rat. In contrast, cyclosporine alone in this dosage produced only 17% mortality and resulted in a similar degree of renal failure. Pair-fed and pair-watered vehicle and saline controls were used. The morphologic changes brought about by the castor oil vehicle of the parenteral cyclosporine solution were qualitatively similar to those brought about by cyclosporine by light microscopy, although the severity of the changes was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum also were seen in other groups. Urine sodium determined by flame photometry and urine chloride determined by Saltex reagent strips tended to be high in the initiation phase of cyclosporine-induced acute renal failure and low in the maintenance phase. In animals that developed acute renal failure following the combination of ischemia and cyclosporine, the initial urine sodium and chloride were significantly correlated with the eventual degree of renal failure. The use of Saltex urine chloride sticks in clinical urine samples showed that the readings correlated well with urine sodium and chloride determined by conventional methods, suggesting that these strips may be useful in making a quick diagnosis in the setting of acute renal failure.
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PMID:Renal morphology and function and urine electrolytes in experimental acute renal failure produced by cyclosporine and ischemia. 384 27

To estimate the renal ischemia-protective effect of saralasin, model studies were performed on rats and dogs. Acute ischemic renal failure was induced in rats by clamping off the vascular pedicle for 90 minutes. When the drug was prophylactically administered before the ischemia episode, a premature increase in post-ischemic plasma urea level and a shortening of survival time of the animals were observed compared with the untreated control. Following auto-transplantation of 24-hour cold-stored dog kidneys, the infusion of saralasin failed to improve renal blood flow (MRBF), glomerular filtration rate (KrCl) and fractional sodium excretion (FENa). On the other hand, the angiotensin blockade with captopril led to an increase in MRBF which was associated, however, with significant decreases in KrCl and FENa. This discrepancy was suggested to be due to a predominant postglomerular vasodilation. The results show that the application of saralasin before renal ischemia may aggravate the loss of renal function whilst the post-ischemic administration of the drug has no substantial effect on the acute failure of transplanted kidneys.
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PMID:[Experimental studies on the modifiability of ischemic acute renal failure by saralasin]. 391 17

Evidence has been presented in the past that muzolimine might act at a localization differently to sulfamoyl-type diuretics and/or with a different or additional mechanism. This is further supported by the fact that at the maximum of the dose-response curves for muzolimine and furosemide in rats, a combination of maximal oral doses still results in significantly higher sodium excretion. To further substantiate that this aspect of muzolimine is of relevance, e. g. for the therapy of acute renal failure, muzolimine treatment by food or implanted osmotic minipumps was employed in an obstructive model of severe renal ischemia in rats. Acute renal ischemia was induced in Wistar rats by clamping the left renal pedicle for 60 minutes with a microsurgery clamp. The right kidney had been removed four days before ischemia. Clearance data were obtained on the first, third and on the ninth to fourteenth days after ischemia in the surviving animals. Renal ischemia resulted in anuria, increased mortality and impaired renal function with histopathologically apparent tubular obstruction in the untreated controls. Treatment with muzolimine by food (in a concentration of 800 ppm for four days) and additional oral gavage one hour prior to ischemia prevented the sequelae of ischemia to a great extent. Similar beneficial effects could be obtained by therapeutic implantation of osmotic minipumps ensuring administration of 0.44 micrograms muzolimine/h per animal. These results in rats further support the suggestion that muzolimine might act differently to sulfamoyl-diuretics. Furthermore, they strongly implicate muzolimine as the diuretic of choice in acute renal failure.
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PMID:Beneficial effect of muzolimine in postischemic acute renal failure in rats. 400 95

In 12 dogs anesthetized with chloralose, angiotensin (angiotensin II amide) given intravenously increased the glomerular filtration rate (GFR) of an ischemic kidney while simultaneously having little effect on the GFR of the contralateral kidney. In the ischemic kidney, in 14 of 30 observations, increments of GFR greater than 100% of mean control GFR (9 ml/min) occurred in response to angiotensin. The magnitude of the increase in GFR produced by angiotensin was independent of dose (range 0.005-0.050 mug/kg per min), the degree of accompanying pressor response, and alterations in renal blood flow (RBF) (electromagnetic flow-meter). In the ischemic kidney, increments of GFR could be produced by sub-pressor doses of angiotensin. Dissociations between increments of GFR and sodium excretion occurred. Equivalent increments of GFR in the ischemic kidney in dogs receiving either 5% glucose in water or 10% mannitol in 0.3% saline were associated with natriuresis only in the latter group: a) as an initial response of the contralateral kidney to renal arterial constriction (RAC) in spite of a concomitant reduction in RBF and an unchanged GFR; b) in the ischemic kidney on giving angiotensin. The natriuresis produced by angiotensin was independent of the magnitude of elevations in blood pressure, altered filtration fraction, and was associated with a further reduction in RBF. After release of RAC in the dogs receiving mannitol, an antinatriuresis was again observed in response to angiotensin. The presence of unilateral renal ischemia allowed the demonstration of a differential action of angiotensin on the GFR of an ischemic and nonischemic kidney. The natriuresis in response to angiotensin requires, in addition to mannitol, the participation of undefined factors invoked by unilateral renal ischemia.
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PMID:Some determinants of the effects of VAL-5-angiotensin II amide on glomerular filtration rate and sodium excretion in dogs. 430 89

Studies of the renin-angiotension system and the effects of pharmacologic blockade have enhanced our understanding of renovascular hypertension. A critical degree of arterial stenosis produces kidney ischemia sufficient to activate this hormonal system, whose actions include vasoconstriction and sodium retention. Accurate clinical evaluation may depend upon recognizing the differences in pathophysiology between "one-kidney" and "two-kidney" forms and the dynamic nature of this condition.
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PMID:Pathophysiology of renovascular hypertension. 638 77

In the present study 1 h of total occlusion of the left renal artery in conscious rats was chosen as experimental model of ischemic acute renal failure (ARF), while the contralateral kidney was left intact. Chronic high dietary sodium intake, acute isotonic saline infusion, or administration of saralasin did not protect from ARF. Furosemide, mannitol, and verapamil converted oliguric into non-oliguric ARF in 100%, 75%, and 60% of the animals, resp. Protection from oliguria and preservation of GFR inversely correlated with the depression of cortical ATP-concentration (control: 1.32 +/- 0.07 mumoles/g wet weight) 6 h after ischemia by 16%, 41%, and 58% in mannitol- and verapamil- treated rats and in untreated rats, resp. At this time, Na-K-ATPase enzyme activities in renal cortex and papilla were unaffected, while enzyme activity in outer medulla was suppressed from 15.4 +/- 1.4 to 9.4 +/- 1.0 mumoles Pi/mg protein h in all groups of animals. The results suggest that in this model of ARF renal ischemia not only affects cellular energy supply in renal cortex but also causes severe structural and functional impairment in the outer medulla, probably leading to tubular obstruction and depression of glomerular function. Pharmacological protection from ischemic oliguric ARF cannot be achieved by prior induction of high urine flow rates alone but depends on the degree of metabolic and functional reserve of the injured tubular epithelium.
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PMID:Renal functional and metabolic studies on the role of preventive measures in experimental acute ischemic renal failure. 641

Models of post-ischemic acute renal failure were prepared in rats. The effects of adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration following renal ischemia on possible changes in renal function and renal cellular metabolism following ischemia were studied using the model. The results obtained revealed the following: 1) Over 40 minute-renal ischemia led to significant lowerings of renal cellular ATP level and energy charge (EC) by as much as 45 to 57% and 4.1 to 7.4% of the control, respectively, at 90 min following re-establishment of renal blood flow. Significant increases in Na+ in renal tissues were observed, but no changes in K+. Further, lactate level in renal tissues tended to increase with prolonged ischemic time by as much as 27 to 31% of the control, with a renal cellular anaerobic metabolism observed. On the other hand, at 24 hr following recirculation of the kidney, plasma creatinine (P-Cr), blood urea nitrogen (BUN) and fraction excretion of sodium (FENa) increased significantly, and creatinine clearance (C-Cr) and urine osmotic pressure decreased significantly, as compared with the control, indicating ischemic acute renal failure. 2) Intravenous injection of ATP-MgCl2 at a dose of 25 mumole/kg and a rate of 1.0 mumol/min after 40 min of renal ischemia led to significant lowerings of P-Cr, BUN and FENa to 36, 35 and 35% of the control (injected with physiological saline solution), respectively, and to significant elevation of C-Cr and urine osmotic pressure by as much as 41 to 31% of the control respectively, at 24 hr after reperfusion. The above results suggested that the ischemic acute renal failure was caused by the decreases in renal cellular ATP and EC with ischemia, resulting in renal cellular metabolic disturbances. It was further suggested that ATP-MgCl2 administered for such a pathological condition could make significant improvements in renal function.
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PMID:[Effect of adenosine triphosphate-magnesium chloride administration for post-ischemic acute renal failure (I)]. 660 69

To determine whether preexistent glomerular injury and the nephrotic syndrome increase renal susceptibility to ischemic renal injury, normal rats and rats with either experimental minimal-change disease (Adriamycin nephropathy) (AN) or membranous nephropathy (passive Heymann nephritis) (PHN) underwent renal functional and histologic studies under either basal conditions or 18 h after bilateral renal artery occlusion (over 30 min). Prior to renal ischemia AN and PHN rats had minimally depressed glomerular filtration rate (GFR), normal (AN) or increased (PHN) renal blood flow (RBF), heavy proteinuria, hypoalbuminemia, decreased urine sodium excretion, extensive glomerular foot process fusion, and intratubular hyalin cast formation. Losses of GFR in response to ischemia were comparable among the three groups of rats (controls, 0.29; AN, 0.28; PHN, 0.25 ml X min-1 X 100 g body wt-1) despite prevailing differences in postischemic hemodynamics. Neither light nor transmission electron microscopy showed any differences in the degree of ischemic renal injury. These results suggest that 1) glomerulopathy and the nephrotic syndrome do not significantly increase renal susceptibility to ischemic renal injury; 2) the syndrome of acute renal failure that occurs in patients with minimal-change glomerulopathy is not due to a marked susceptibility of these kidneys to clinically occult ischemic events; and 3) foot process fusion is probably not a pathophysiologically significant lesion in ischemic acute renal failure, as previously suggested.
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PMID:Glomerulopathy does not increase renal susceptibility to acute ischemic injury. 670 61

To investigate the possible protective effect of Ca2+ blockers in ischemic acute renal failure (ARF), verapamil, in a dose of 10 micrograms/kg body wt/min was administered for 100 min, starting 15 min before the total occlusion of the left renal artery after right nephrectomy in rats. Mean 24-hr creatinine clearance, blood urea, and serum creatinine levels, 24 hr after declamping, were used as a measure of kidney function. These values which were 135 +/- 1.9 microliter/min, 231 +/- 22 mg%, and 2.25 +/- 0.22 mg%, respectively, in the untreated rats, were found to be significantly different, i.e., 326.3 +/- 33.2 microliter/min, P less than 0.001, 112 +/- 25 mg%, P less than 0.001, and 1.26 +/- 0.28 mg%, P less than 0.01, respectively, in the verapamil-treated animals. Increased 24-hr total urine creatinine, sodium, osmolality, and a lower fractional excretion of sodium were also observed in the verapamil-treated rats with ARF. The combination of propranolol 1 mg/kg body wt/min and verapamil 10 micrograms/kg body wt/min for 100 min had no additive effect on renal function. In another group of ARF rats in which verapamil was started after declamping, no alleviating effect was observed. It is concluded that verapamil, an inhibitor of cellular membrane transport, when given prior to the renal ischemia, offers a partial but significant protection in this model of ischemic ARF.
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PMID:Beneficial effect of verapamil in ischemic acute renal failure in the rat. 684 46

The urinary excretion of four enzymes (alkaline phosphatase: AP, leucine aminopeptidase: LAP, lactate dehydrogenase: LDH, muramidase: M) was measured in unanesthetized adult male Wistar rats within 48 h after either a single injection of mercuric chloride (HgCl2) (0.5-1.0 mg x kg-1), or of gentamicin (2.5-25 mg x kg-1), or of tobramoycin (2.5-25 mg x kg-1), or after 30 min of clamping of both renal arteries. Glomerular filtration rate (GFR), TmPAH, plasma urea, urinary protein and sodium excretion were measured simultaneously. The excretion of AP, LAP and LDH, but not that of M, increased significantly above control levels after renal ischemia or the nephrotoxic agents; the increase was dose-related after HgCl2. GFR was not depressed, but TmPAH decreased after the higher doses of the toxic agents. Though more sensitive for detecting minor grades of acute renal damage than function tests, measurements of urinary enzyme excretion were fraught with large inter-individual variation, and variable time-course of changes in different types of renal damage. Short-term exposure (3 months) to phenylmercuric acetate was associated with a significant decrease of the urinary excretion of AP, and of LAP, and of AP activity measured histochemically in proximal tubular cells.
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PMID:Urinary enzyme excretion and changes in renal functions induced by toxic substances or by renal ischemia in rats. 693 3


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