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)

The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml.kg-1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure. In healthy rats saralasin (6 microgram.kg-1.min-1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng.kg-1.min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.
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PMID:Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat. 60 Mar 26

One to four weeks after the left renal artery was clipped and the contralateral kidney was left untouched in Sprague-Dawley rats (two-kidney Goldblatt preparation), the clips were removed under ether anesthesia and 10 ml/kg body wt of either 150 mM NaCl (control) or 50% glycerol in water (experimental) were injected intramuscularly. The next day the rats were anesthetized (sodium pentobarbital) and the renal function of both kidneys was measured, after which the renal cortical renin content was measured by incubation of tissue homogenate with angiotensinase-free rat renin substrate. Radioimmunoassay was used to determine the rate of angiotensin I production. Compared with controls, both kidneys of glycerol-injected rats had reduced GFR (left 28, right 18% of controls), increased percentage of fractional water excretion (left 5, right 6 times controls), and increased percentage of fractional Na excretion (left 3, right 4 times controls). Despite large differences in renal renin (left 28, 676, right 1,329 ng angiotensin I/h per mg protein), the extent of renal failure produced by glycerol was equal in the left and right kidneys. These results are inconsistent with the hypothesis that renal renin content is directly related to the severity of glycerol-induced renal failure in rats.
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PMID:Glycerol-induced acute renal failure in the two kidney Goldblatt rat. 91 Sep 21

The renal effects of furosemide in acute renal failure of the rat were studied using clearance and micropuncture techniques. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml/kg). Functional impairement of the glycerol treated animals consisted of a decrease in urinary sodium excretion, renal blood flow, total kidney GFR and effective filtration pressure of superficial nephrons. Effective filtration pressure was calculated from proximal free flow and stop flow pressure measurements. In contrast to control animals furosemide did not increase urine volume during acute renal failure due to a marked fall in GFR. Renal blood flow, as measured by an electromagnetic flowmeter, also decreased after furosemide in glycerol treated rats and increased in control animals. Furosemide reduced effective filtration pressure during acute renal failure to almost zero, whereas in control animals effective filtration pressure virtually remained constant.
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PMID:Renal effects of furosemide in glycerol induced acute renal failure of the rat. 98 44

We investigated the tubular action of endothelin in rat nephron segments. The effects of endothelin on arginine vasopressin (AVP)-, parathyroid hormone-, glucagon-, calcitonin-, and isoproterenol-dependent cAMP accumulation were studied. The following nephron segments were microdissected: glomerulus (Gl), proximal convoluted tubule (PCT), cortical and medullary thick ascending limbs of Henle's loop (cTAL and mTAL, respectively), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). Endothelin dose dependently (10(-8)-10(-10)M) inhibited AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD. This effect was independent of the presence or absence of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, Ca channel blocker nicardipine, or indomethacin, but was abolished in the presence of protein kinase C inhibitor H-7. Protein kinase C stimulator dioctanoyl glycerol mimicked the effect of endothelin. On the other hand, endothelin had no inhibitory effect on AVP-dependent cAMP accumulation in cTAL or mTAL, parathyroid hormone-dependent cAMP accumulation in Gl and PCT, or glucagon-, calcitonin-, and isoprotereol-dependent cAMP accumulation in OMCD. We conclude that endothelin specifically inhibits AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD through activating protein kinase C. This effect possibly has a role in maintaining urine volume to counteract the decrease in GFR caused by endothelin itself.
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PMID:Effects of endothelin on peptide-dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat. 169 79

The role of protein kinases in renal noradrenergic stimulation was examined using sphingosine, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperizine (H7), using sphingosine, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperizine (H7), or staurosporine to inhibit the responses to norepinephrine (NE, 60 nM) in isolated perfused rat kidneys. Sphingosine (20 mumol/L) increased the noradrenergic vasoconstrictor response. H7 (10 mumol/L) partially blocked the immediate vasoconstrictor response and completely inhibited it after 2 min without altering the antinatriuretic and antilithuretic responses. H7 also blocked the increase in free water produced by NE, which is consistent with the inhibition of protein kinase A linked to beta-adrenergic stimulation. Staurosporine (10 nmol/L) partially inhibited noradrenergic vasoconstriction and antinatriuresis, and it completely blocked the depression of gluconeogenic responses to NE in pyruvate-perfused kidneys. To examine the role of diacylglycerol and protein kinase C in the renal responses to NE, we used oleoyl-acetyl-glycerol (OAG, 50-100 microM) or phorbol-12-myristyl-13-acetate (TPA, 5-50 nM). TPA slowly vasoconstricted the kidney and reduced GFR and fractional Na+, Li+, and free water excretion. Amiloride (1 mM) prevented the TPA responses. OAG mimicked the effects of TPA except that vasoconstriction occurred more rapidly and was brief. Both TPA and OAG acted like alpha 1-adrenergic agonists. These results indicate that diaclyglycerol and protein kinase are involved in the prolonged effects of NE on vasoconstriction. GFR, and proximal tubular reabsorption.
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PMID:Diacylglycerol and protein kinase mediated noradrenergic responses in perfused rat kidneys. 239 Jul 42

Renal cortical, medullar and papillary T1 and T2 relaxation times were measured in rats with normal (n = 13) and impaired renal function (n = 11) with a Bruker Multispec, 20 MHz at 37 degrees C. In one group of seven rats, decreased renal function was obtained by 50% glycerol solution administration (10 ml/kg-body weight) 24 hours before the experiment, while in another group of four rats the renal function was decreased, by ureteral ligation for 72 hours. Immediately after the excision of one kidney, Gadolinium-DTPA (70 mumole/kg body weight) was injected intravenously. The second kidney was excised 5 min later. From the T1 and T2 relaxation times measured in the cortex, medulla, and papilla, their respective ratios before and after GdDTPA administration were calculated and correlated with GFR determined by creatinine clearance (Ccr range was between 0 and 850 microliters/min/g kidney weight). For T1: the ratios in the cortex, medulla, and papilla the correlation coefficients were r = 0.81 (p less than 0.001), r = 0.85 (p less than 0.001), and r = 0.87 (p less than 0.0001), respectively. The respective correlation coefficient r values for T2 were r = 0.38 (NS), r = 0.76 (p less than 0.001), and r = 0.73 (p less than 0.001). The present study indicates that a combination of MR measurements, with and without GdDTPA paramagnetic enhancement, can offer a new possibility for obtaining information on renal function and suggest the possibility of concomitant anatomo functional magnetic resonance imaging.
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PMID:Paramagnetic enhanced proton magnetic resonance measurement in rats: correlates with renal function. 337 84

To assess the effects of altered renal function on Na-K-ATPase, the following groups of rats were studied: 1. rats with suprarenal vena cava ligation (SVCL), la. DOCA-treated rats with SVCL, 2. rats with infrarenal vena cava ligation (IVCL), 3. rats with glycerol-induced acute renal failure, 4. rats with bilateral ureteric ligation, and 5. K-exalate-treated rats with SVCL. In group 1, acute renal failure with hyperkalemia developed and medullary Na-K-ATPase increased from 95 +/- 5 in control to 155 +/- 7 mumol Pi/mg prot/h, P less than 0.001, DOCA did not prevent the increase of Na-K-ATPase. In group 2, medullary Na-K-ATPase decreased from 130 +/- 10 in control to 88 +/- 7, P less than 0.01, in rats with IVCL. In group 3, cortical Na-K-ATPase decreased from 55 +/- 5 to 27 +/- 6, P less than 0.02. In group 4, Na-K-ATPase was unchanged. In group 5, maintenance of normokalemia prevented the rise in Na-K-ATPase. These experiments demonstrated a K-dependent activation of medullary Na-K-ATPase after SVCL but not in other forms of renal failure. Because SVCL diminishes drastically GFR per nephron, the present findings imply that increased loads of Na and K per nephron are not a prerequisite for an increase in medullary Na-K-ATPase. Hyperkalemia in presence of increased renal venous pressure seems to be causally related to the rise in medullary Na-K-ATPase activity.
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PMID:Renal function and Na-K-ATPase in rats after suprarenal ligation of inferior vena cava. 612 57

The purpose of this study was to examine proximal and distal tubular function in rats with nonoliguric, myohemoglobinuric acute renal failure (ARF). ARF was induced with glycerol (50%, 10 ml/kg of body wt, i.m.), and renal function was studied 24 hours after glycerol or saline (controls) injection. Glycerol injection caused a 50 to 90% depression in GFR and a significant rise in blood urea nitrogen concentration. Animals with ARF exhibited glycosuria with normal blood sugar levels and a striking depression in tubular glucose reabsorption per milliliter of GFR. The capacity to reabsorb (mEq/liter GFR) was intact at normal blood bicarbonate levels, but was markedly depressed when blood bicarbonate was raised. The tubular maximum for para-aminohippurate (PAH) secretion and the renal extraction fraction of PAH were strikingly depressed in rats with ARF. Distal acidification as assessed by the urine-to-blood gradient of PCO2 (UB PCO2) was normal both during maximal alkalinization of the urine with bicarbonate (urine pH, approximately 7.8) or during neural phosphate infusion (urine pH, approximately 7.0). Net acid excretion per milliliter GFR and minimal urine pH (less than 5.5) following 3 days of ammonium chloride ingestion was similar in control and ARF animals. Potassium excretion was intact in maximal urinary osmolality were significantly altered in animals with ARF. Cortical and outer medullary Na-K-ATPase specific activities were significantly depressed in ARF rats. This occurred as a consequence of enzyme loss and not secondary to alterations in enzyme kinetics of absolute tubular sodium reabsorption. Light and electron microscopy showed diffuse proximal tubular damage, whereas glomeruli and distal tubules were intact. These data demonstrate that glycerol injection produces a diffuse proximal tubular transport defect associated with histologic and enzymatic alterations.
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PMID:Renal tubular function in glycerol-induced acute renal failure. 678 13

Systemic and renal hemodynamics and body fluid volumes were evaluated in 48-hour uninephrectomized (UNX) and sham-operated (SO) rats, 3 h after glycerol-induced acute renal failure (ARF). UNX rats showed a 20% increase in cardiac output (CO) and renal blood flow (RBF) and a 20% decrease in total peripheric resistance (TPR) and renal vascular resistance (RVR) with respect to the control rats. There was no difference in body fluid volumes. 3 h after ARF induction UNX rats showed a minor decrease in RBF and GFR and a minor increase in RVR when compared with the control rats. CO decreased to similar levels in both UNX and SO rats. Mean arterial pressure and TPR increases were observed in UNX and SO rats but these increases were higher in the UNX than in the SO rats. Plasma and extracellular volumes were reduced in both groups of rats. The partial protection afforded by the renal mass reduction against the glycerol-induced ARF seem to be explained by the minor decrease in RBF and the lesser increase in RVR exhibited by the UNX rats after ARF induction.
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PMID:Role of hemodynamic alterations in the partial protection afforded by uninephrectomy against glycerol-induced acute renal failure in rats. 708 34

21-aminosteroids ("lazaroids") have recently excited much interest by virtue of their ability to inhibit lipid peroxidation in vitro and to protect against neural injury in vivo. We tested the effect of these compounds in models of heme protein-mediated renal injury in vitro and in vivo. We devised an in vitro model of heme protein-induced toxicity in which renal epithelial cells were exposed to heme proteins for one hour, after which they were subjected to glutathione depletion by 1-chloro-2,4-dinitrobenzene (CDNB). This model was associated with more than a threefold increase in lipid peroxidation (as measured by thiobarbituric acid reactive substances, TBARS) and a marked reduction in cellular glutathione content. In this model, 21-aminosteroids virtually prevented cytotoxicity as measured by the 51-chromium release assay, and significantly reduced TBARS in a dose-dependent manner. Catalase was partially protective in this model, thereby indicating hydrogen peroxide-dependent toxicity. While pursuing mechanisms accounting for enhanced cellular generation of hydrogen peroxide, we uncovered the first direct evidence that the heme prosthetic group per se directly stimulates cellular generation of hydrogen peroxide; complementing these findings is the remarkable efficacy of 21-aminosteroids in protecting against cytotoxicity induced by hydrogen peroxide. We also tested the capacity of 21-aminosteroids to protect against heme protein-mediated renal injury in vivo. Prior administration of 21-aminosteroids attenuated reductions in GFR and renal blood flow rates following the systemic infusion of methemoglobin in normal rats. 21-aminosteroids also attenuated renal injury observed over three successive days in the glycerol model of heme protein-mediated injury when this model was induced at a higher dose of glycerol (8 ml/kg body wt) but not at a lower dose (5 ml/kg body wt). We conclude that 21-aminosteroids protect against heme protein-mediated renal injury in vitro and in vivo. We suggest that these compounds are potentially useful in such clinical conditions as rhabdomyolysis, intravascular hemolysis and renal injury associated with hemoglobin-based red blood cell substitutes.
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PMID:Heme protein-mediated renal injury: a protective role for 21-aminosteroids in vitro and in vivo. 772 46


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