Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute renal failure in the rat was induced by occluding the left renal artery for 1 hour. The kidneys were examined 1, 3, 10, and 40 days after temporary ischemia. Inulin clearance was essentially zero in oligoanuric kidneys on days 1 and 3, and regained 14% and 63% of the control value on days 10 and 40, respectively. Mean cortical blood flow remained almost constant at 75% of control up to day 10 and normalized subsequently on day 40. Renal oxygen consumption during anuria on days 1 and 3 was 53% and 46% of the control value and increased thereafter concurrently with the restoration of renal function. With a single linear correlation being assumed to exist between sodium reabsorption and oxygen consumption for all kidneys, the sodium reabsorption and oxygen consumption for all kidneys, the sodium transport estimated from oxygen consumption on day 1 was about 40% of control value. The difference between the sodium transport calculated from oxygen consumption and that from inulin clearance decreased with time in the recovery phase. The results indicate only a partial reduction of GFR due to the reduced blood flow in this model. The data are consistent with the hypothesis that tubular leakage and tubular obstruction play an important role in the loss of renal function during the manifestation of acute renal failure.
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PMID:Renal hemodynamics and oxygen consumption during postischemic acute renal failure in the rat. 723 Jun 17

The morphological factors contributing to the reduction GFR in an early phase of NE-induced ARF (0.75 microgram/kg/min) were evaluated by comparing renal morphology at the end of NE infusion with that 2 hr later in unilaterally nephrectomized dogs. GFR 2 hr after NE infusion was reduced to 50% of the preinfusion level in a 30 min infusion group (N = 6), to 13% in a 60 min infusion group (N = 7), and to 2% in a 120 min infusin group (N = 5). On the other hand, simultaneous RBF was not significantly reduced in any group. Dilated PT lumina filled with eosinophilic granular materials in paraffin sections fixed in Zenker-Formol or with impacted swollen blebs in Epon sections fixed in diluted Karnovsky's solution and osmium were found diffusely immediately following 60 and 120 min NE infusion, but patchily after 30 min infusion. Similar changes were found 2 hr after the infusion, except that some PTs came to have dilated but transparent lumina in the 60 and 120 min NE infusion groups. Electron microscopic studies revealed that a part of the membrane-bounded cytoplasm of PT cells extruded into the tubular lumen and became impacted swollen blebs during NE-induced ischemia. There was no prominent foot process fusion in any group. It is concluded that the tubular obstruction by impacted swollen blebs generated in PT during ischemia is a major factor responsible for the reduction in GFR in the early phase of NE-induced ARF.
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PMID:Morphological changes in an early phase of norepinephrine-induced acute renal failure in unilaterally nephrectomized dogs. 741 55

Nitric oxide (NO) is involved in the regulation of renal perfusion and glomerular hemodynamics under basal conditions. We examined the hypothesis that L-arginine-derived NO modifies ischemic acute renal failure (ARF) in the rat. After a basal period ischemia was induced by clamping of both renal arteries (40 min). Thereafter, in the reperfusion period, we intravenously infused L-arginine (Arg, 300 mg/kg/60 min), or L-monomethylarginine (MeArg, 30 mg/kg/60 min), or Arg + MeArg (300 mg/kg/60 min, 30 mg/kg/60 min, resp.). Besides monitoring of urinary flow rate and arterial blood pressure, and determination of sodium excretion, glomerular filtration rate (GFR, mL/min/100 g) was estimated at the end of the infusion period and again after another 30 and 120 min by inulin clearance (fluorescence-marked inulin). In the basal period GFR showed no differences between the groups (Arg: 0.86 +/- 0.07, MeArg: 0.92 +/- 0.06, Arg + MeArg: 0.89 +/- 0.08, control: 0.84 +/- 0.07). At 180 min after the beginning of the reperfusion period, GFR was 0.13-0.02 in the control group. After administration of Arg, a remarkable and persistent increase in GFR was observed (0.28 +/- 0.03), whereas infusion of MeArg showed no significant effects (0.13 +/- 0.04). Combined administration of Arg + MeArg revealed a moderate increase of GFR (0.19 +/- 0.05), ranging between the Arg and the control group. Also, 60 and 90 min after the beginning of the reperfusion period, the highest values for GFR were obtained in the Arg group. We conclude that in this model of ischemic ARF in the rat, L-arginine-derived NO is capable of improving renal function. These data underline the regulatory role of the L-Arg-NO pathway for renal function, not only under normal conditions, but also in ARF.
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PMID:Role of L-arginine-derived NO in ischemic acute renal failure in the rat. 753 65

Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME). Chronic treatment with L-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 +/- 16 mmHg) as compared to controls (155 +/- 4 mmHg). Animals receiving simultaneously L-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56 +/- 0.73 ml.kg-1.min-1) and renal plasma flow (RPF: 6.93 +/- 1.70 ml.kg-1.min-1) as compared to control (GFR: 7.29 +/- 0.69, RPF: 21.36 +/- 2.33 ml.kg-1.min-1). Addition of ramipril prevented L-NAME-induced reduction in GFR and renal plasma flow. L-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with L-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency. 753 99

Amphotericin B (AmB) has been in clinical use for more than 30 yr but has remained the most effective drug for treatment of serious fungal infections. Its use has increased in recent years, as the result of increases in aggressive intensive care support and increased numbers of immunocompromised patients. Nephrotoxic manifestations are common, and this is the major factor limiting the clinical use of the drug. A number of recent studies have contributed to a better understanding of the mechanism by which AmB exerts its nephrotoxic effect. AmB alters cell membrane permeability and probably as a consequence alters tubular and vascular smooth muscle cell function, leading to various tubular transport defects and vasoconstriction. Decreased RBF appears to play a major role in AmB-induced reduction GFR, and recurrent ischemia may be the basis of permanent structural nephrotoxic effects. Salt loading is the only measure proven by controlled prospective study to ameliorate AmB nephrotoxicity in humans. Liposomal AmB and the formulation of an emulsion of AmB in lipid may provide a protective effect based on altering the affinity of AmB for mammalian cell membranes, while preserving high efficacy against fungal cells. However, further studies are needed to evaluate the efficacy and safety of these new AmB formulations.
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PMID:Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties. 757 79

Because chronic iron overload can cause organ injury in hemochromatosis and because iron participates in injury during renal ischemia-reperfusion, the effect of mild subacute renal iron loading on the susceptibility to ischemic acute renal failure was evaluated. Male Sprague-Dawley rats were injected with iron nitrilotriacetate (1 mg iron/kg BW i.p. daily) for 5 days. Controls were instead injected with nitrilotriacetate. Seventy-two hours later animals were subjected to 40-min renal artery ischemia. Iron loading produced a 28% increase in kidney iron content without any change in baseline renal function (plasma creatinine) or histology. Ischemic renal injury was far more severe in iron-loaded animals. Plasma creatinine 24 and 48 h after ischemia was significantly higher in iron-loaded rats (3.3 and 3.4 vs. 2.2 and 0.8 mg/dL) and GFR was significantly lower in iron-loaded rats (0.30 vs. 0.78 mL/min). In addition, iron-loaded rats showed a dramatically greater extent of damage by histologic evaluation using a semiquantitative scoring method. Therefore, a small increase in renal iron content greatly increased renal injury after an ischemic insult. These findings may be relevant to human renal disease because there is accumulating evidence of renal iron accumulation in a variety of proteinuric and chronic renal diseases.
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PMID:Iron loading enhances susceptibility to renal ischemia in rats. 793 55

The aim of this study was to gain further insight into the greater susceptibility to acute ischemic renal failure (ARF, 30 min of renal arteries clamping) of old rats (O, 18 months) as against young rats (Y, 3 months). All the rats ate a hypoproteic diet (14% of casein) to avoid age-related glomerulosclerosis in O. Basal renal dynamics was similar in O and Y (Groups CON). One day after ARF, the decrease in GFR was more severe in O than in Y (-82% and -57% vs. respective CON, P < 0.05), due to a greater rise of RVR in O (+258%) than in Y (+104%). The histological renal damage after ischemia was comparable in the two groups with ARF. Five days after ARF, the recovery of renal function was characterized by a slower rise of GFR in O than in Y. In two further groups, two different scavengers of oxygen-free radicals, dimethylthiourea (DMTU) and superoxide dismutase (SOD), were administered at the time of arterial occlusion. DMTU had protective effects in Y but not in O (delta GFR was -28% and -72%, respectively); in contrast, SOD was more effective in O (delta GFR = -58%) than in Y rats (delta GFR = -40%). To test the hypothesis that such a difference was related to the capacity of SOD to increase the levels of nitric oxide (NO), four more groups of Y and O rats were pretreated with L-arginine (ARG), precursor of NO, in tap water (1.5%). No difference in renal dynamics was detected in basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional versus structural changes in the pathophysiology of acute ischemic renal failure in aging rats. 807 48

After 45-min bilateral warm renal ischemia lethality amounted to 45% and 82% in 55- and 20-day-old rats, respectively (n = 176). Lethality rates were not significantly different after 20-min unilateral ischemia followed by contralateral nephrectomy after 24 hours (34 vs. 48% in young vs. adult rats; n = 168). The latter experimental approach was used to characterize age dependent differences in the susceptibility to ischemia. The degree of postischemic renal damage was the highest at the 1st and 2nd days after ischemia; at this time, lethality rates were similar in young and adult rats. However, urea concentration in serum was significantly more enhanced in young animals whereas that of creatinine was increased to the same extent in both age groups. The increase in protein excretion into urine was similar in young and adult rats, too. Furthermore, urine flow rates and GFR were significantly diminished after ischemia, independent of age. However, excretion of Na+ and K+ was distinctly more depressed in immature individuals. Finally, the glutathione content in kidney tissue of both age groups was reduced and lipid peroxidation was significantly higher after ligation of the renal arteries. The relative changes were similar in both age groups although the glutathione content was significantly lower in 20-day-old control rats. 4-5 days after ischemia, most parameters returned to baseline values. In 55-day-old rats, 45-min ischemia has more severe consequences on renal function compared to 20-min ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of methods indicating higher susceptibility of immature rats to renal ischemia. 832 66

To investigate the potential pathogenetic and therapeutic roles of thromboxane A2 (TXA2) and its receptor blockade, respectively, in the early phase of ischemic acute renal failure (ARF), renal function, TXB2 excretion, and the effects of the specific TXA2 receptor antagonist sulotroban (SU) in a model of unilateral renal artery occlusion in conscious female Sprague-Dawley rats were studied. Occlusion of the left renal artery for 1 h in untreated (i.e., vehicle-treated) rats (N = 8) resulted in oliguric ARF. In SU-treated rats (N = 8), the drug was given as an i.v. bolus of 5 mg/kg body wt, followed by a continuous infusion of 0.5 mg/min.kg body wt from 1 h before and during ischemia and for 6 h after reflow. After 1 h of ischemia, urine volume of left ischemic kidneys from untreated rats had decreased from 13.2 +/- 2.8 to 1.0 +/- 0.3 and 0.5 +/- 0.2 microL/min.100 g at 2 and 6 h of reflow, respectively, and GFR had decreased from 0.32 +/- 0.04 mL/min.100 g body wt to undetectable values. At 6 h of reflow, medullary Na-K-ATPase was slightly (P < 0.05) reduced in left ischemic kidneys, whereas medullary and papillary enzyme activities were compensatorily increased (P < 0.01) in right intact kidneys. The ADP/O ratio of cortical mitochondria was 41% (P < 0.05) and ATP synthesis was 77% (P < 0.01) lower than in right intact kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of thromboxane A2 receptor blockade on oliguric ischemic acute renal failure in conscious rats. 840 69

Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygen-derived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n = 6), the following treatment groups were investigated. Allopurinol (n = 7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n = 6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n = 7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group. Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion). At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals.
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PMID:Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs. 845 8


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