The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats

1987 ◽  
Vol 65 (7) ◽  
pp. 1491-1495 ◽  
Author(s):  
Jen-Jar Lin ◽  
Paul C. Churchill ◽  
Anil K. Bidani
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Plasma Flow ◽  
Left Kidney ◽  
Artery Occlusion ◽  
Control Group ◽  
Left Renal Artery ◽  
Initiation Phase ◽  
Adenosine Receptor Antagonist ◽  
Arterial Blood

Several previous observations support the hypothesis that increased adenosine production and release mediate, at least in part, the reductions in renal blood flow and glomerular filtration rate in ischemic acute renal failure (ARF). If this hypothesis is correct, dipyridamole should potentiate these changes, since it blocks cellular adenosine uptake, thereby increasing the concentration and potentiating the effects of extracellular adenosine. Moreover, theophylline should block the effects of dipyridamole, since it is an adenosine receptor antagonist. These predictions were tested in three groups of anesthetized rats. All rats were subjected to 30 min of left renal artery occlusion; 30 min after relieving the occlusion, a 45-min clearance period was begun. The control group was given saline i.v.; the two experimental groups received either dipyridamole (24 μg∙min−1∙kg−1) or dipyridamole plus theophylline i.v. (111 μmol/kg as a prime, 1.1 μmol∙min−1∙kg−1 as an infusion). In the control group, the previously ischemic left kidneys exhibited decreased clearances of para-aminohippurate and inulin (CPAH and CIn), filtration fraction (FF), and urine/plasma inulin concentration (U/PIn), and increased urine flow (V), Na excretion (UNaV), and fractional Na excretion (FENa) in comparison with the contralateral right kidney. Dipyridamole pretreatment did not affect the right kidney, but it intensified the reductions in left kidney CPAH, CIn, and FF. Theophylline blocked all these effects of dipyridamole on the left kidney, and increased renal plasma flow (CPAH/PAH extraction), despite a decrease in systemic arterial blood pressure. These results are further support for the hypothesis that adenosine mediates, at least in part, the hemodynamic changes in postischemic ARF in rats.

Acute cyclosporine-induced renal vasoconstriction: lack of effect of theophylline

1990 ◽  
Vol 258 (1) ◽  
pp. F41-F45
Author(s):  
P. C. Churchill ◽  
N. F. Rossi ◽  
M. C. Churchill ◽  
A. K. Bidani ◽  
F. D. McDonald
Keyword(s):  
Renal Plasma Flow ◽  
Left Kidney ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Adenosine Receptor Antagonist ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Group 1

Both acute and chronic administration of cyclosporine A (CSA) lead to renal vasoconstriction, but the mechanism is not fully understood. The present studies were designed to explore the possible role of adenosine in acute CSA-induced renal vasoconstriction in rats. Six groups of anesthetized Sprague-Dawley rats were studied using standard clearance techniques: group 1 rats were controls; groups 2, 4, and 6 received CSA intravenously at 20, 30, and 40 mg.h-1.kg body wt-1, respectively; groups 3 and 5 were identical to groups 2 and 4 except that a priming injection of theophylline was given (56 mumol/kg body wt) and theophylline was included in the intravenous infusate (0.56 mumol.min-1.kg body wt-1). CSA produced acute and concentration-dependent reductions in renal plasma flow (left kidney) and in the clearances of p-aminohippuric acid and inulin (both kidneys). Except in group 6, these changes were observed in the absence of a decrease in arterial blood pressure, demonstrating that CSA produced an acute and concentration-dependent increase in renovascular resistance. Theophylline not only failed to block CSA-induced renal vasoconstriction, if anything, it potentiated it. Because theophylline is an adenosine receptor antagonist, these findings contradict the hypothesis that adenosine mediates acute CSA-induced renal vasoconstriction.

Erythropoietin enhances recovery from cisplatin-induced acute renal failure

1994 ◽  
Vol 266 (3) ◽  
pp. F360-F366 ◽  
Author(s):  
N. D. Vaziri ◽  
X. J. Zhou ◽  
S. Y. Liao
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Functional Recovery ◽  
Deficiency Anemia ◽  
Control Group ◽  
Cortical Tissue ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Significant Difference ◽  
Epo Deficiency

Acute renal failure (ARF) is associated with erythropoietin (EPO) deficiency anemia. The present study was designed to determine whether the course of ARF can be altered by preventing EPO deficiency and the associated anemia. Sprague-Dawley rats were injected with a single dose of cisplatin (CP), 7 mg/kg intraperitoneally, and randomized into recombinant EPO-treated (EPO), placebo-treated (control), recombinant EPO-treated pair-fed (EPO-PF), and EPO-treated anemic (EPO-anemic) groups. They were then treated with daily injections of recombinant EPO, 100 U/kg, or placebo for 9 days. Animals in the EPO-anemic group received daily phlebotomies gauged to maintain hematocrits equal to those in the control group. Rats in the EPO-PF group were pair fed with the controls. The control and EPO-anemic groups showed a fall, whereas the EPO and EPO-PF groups showed a rise in hematocrit on day 9. Although blood volume on day 9 was significantly greater in the EPO group than in either the EPO-anemic group or the control group, it was comparable in the latter groups. An equally severe reduction in creatinine clearance (CCr) was found in all groups on day 4. However, measurements of CCr and inulin clearance on day 9 revealed a significantly greater functional recovery in the EPO, EPO-PF, and EPO-anemic groups than in the controls. The enhanced functional recovery with EPO administration was accompanied by an increased tubular regeneration and [3H]thymidine incorporation in the cortical tissue. No significant difference was found in either cortical tissue iron content or arterial blood pressure in the study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Maintenance and recovery stages of postischemic acute renal failure in humans

2002 ◽  
Vol 282 (2) ◽  
pp. F271-F280 ◽  
Author(s):  
Deepa Ramaswamy ◽  
Geraldine Corrigan ◽  
Catherine Polhemus ◽  
Derek Boothroyd ◽  
John Scandling ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Control Group ◽  
Hydraulic Pressure ◽  
Structural Controls ◽  
Single Nephron

Postischemic injury in 38 recipients of 7-day-old cadaveric renal allografts was classified into sustained ( n = 15) or recovering ( n = 23) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of long-standing allografts that functioned optimally ( n = 16) and living transplant donors undergoing nephrectomy ( n = 10) served as functional and structural controls, respectively. A combination of physiological and morphometric techniques were used to evaluate glomerular filtration rate and its determinants 1–3 h after reperfusion and again on day 7 to elucidate the mechanism for persistent hypofiltration in ARF that is sustained. Glomerular filtration rate in the sustained ARF group on day 7 was depressed by 90% (mean ± SD); the corresponding fall in renal plasma flow was proportionately less. Neither plasma oncotic pressure nor the single-nephron ultrafiltration coefficient differed between the sustained ARF and the control group, however. A model of glomerular ultrafiltration and a sensitivity analysis were used to compute the prevailing transcapillary hydraulic pressure gradient (ΔP), the only remaining determinant of ΔP. This revealed that ΔP varied between 27 and 28 mmHg in sustained ARF and 32–38 mmHg in recovering ARF on day 7 vs. 47–54 mmHg in controls. Sustained ARF was associated with persistent tubular dilatation. We conclude that depression of ΔP, perhaps due partially to elevated tubule pressure, is the predominant cause of hypofiltration in the maintenance stage of ARF that is sustained for 7 days.

Aminophylline ameliorates glycerol-induced acute renal failure in rats

1983 ◽  
Vol 61 (6) ◽  
pp. 567-571 ◽  
Author(s):  
K. Bidani ◽  
P. C. Churchill
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Serum Creatinine ◽  
Biological Fluids ◽  
Protective Effects ◽  
Initiation Phase ◽  
Adenosine Receptor Antagonist ◽  
Phase 0 ◽  
Series Of Experiments

The effect of aminophylline (theophylline complexed with ethylenediamine) on the severity of glycerol-induced myohemoglobinuric acute renal failure was examined in rats. In the first series of experiments, one group of rats received twice daily injections of aminophylline following the induction of acute renal failure, and a second group (controls) received twice daily injections of saline. Only one of the aminophylline-injected rats but five of the saline-injected rats died during the 3-day follow-up period. Moreover, mean serum creatinine was lower in the aminophylline-injected rats than in the saline-injected controls on each of the 3 days, demonstrating that aminophylline reduced the renal functional impairment. In the second series, single injections of aminophylline were given at the time of glycerol injections or 3, 6, or 24 h later. As assessed by mean serum creatinine during the 3-day follow up, even single injections had protective effects if given during the initiation phase (0–3 h after glycerol). Since aminophylline dissociates into theophylline in biological fluids, and since theophylline is an adenosine-receptor antagonist, these observations are consistent with the hypothesis that adenosine plays a pathogenic role in myohemoglobinuric acute renal failure in rats.

Complete Resolution of Acute Renal Failure after Left Renal Artery Angioplasty and Stent Placement for Total Renal Artery Occlusion

Cardiology ◽  
2006 ◽  
Vol 108 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Arshad Rehan ◽  
Yassar Almanaseer ◽  
Devang M. Desai ◽  
Arshad Ali ◽  
Hiroshi Yamasaki
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Artery ◽  
Stent Placement ◽  
Complete Resolution ◽  
Artery Occlusion ◽  
Left Renal Artery ◽  
Renal Artery Occlusion

Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-1 overproduction

2002 ◽  
Vol 103 (s2002) ◽  
pp. 434S-437S ◽  
Author(s):  
Masanori TAKAOKA ◽  
Mikihiro YUBA ◽  
Toshihide FUJII ◽  
Mamoru OHKITA ◽  
Yasuo MATSUMURA
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Dysfunction ◽  
Tissue Injury ◽  
Male Rats ◽  
Left Renal Artery ◽  
Protective Effects ◽  
Endothelin 1 ◽  
Ischaemia Reperfusion

We investigated whether the treatment with 17β-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17β-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17β-oestradiol (20 or 100µg/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17β-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17β-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.

The Protective Effect of γ-Glutamyl l-Dopa on the Glycerol Treated Rat Model of Acute Renal Failure

1983 ◽  
Vol 65 (2) ◽  
pp. 159-164 ◽  
Author(s):  
I. F. Casson ◽  
D. A. Clayden ◽  
G. F. Cope ◽  
M. R. Lee
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Protective Effect ◽  
Rat Model ◽  
Fold Increase ◽  
Plasma Creatinine ◽  
Control Group ◽  
Creatinine Excretion ◽  
Urine Creatinine ◽  
Before And After

1. γ-Glutamyl l-dopa, a renal pro-drug for dopamine, was administered to rats before and after injection of glycerol, and to a control group which received water in place of glycerol. A third group of rats was given glycerol but no γ-glutamyl l-dopa. 2. The plasma creatinine in rats given γ-glutamyl l-dopa and glycerol was significantly lower than in rats receiving glycerol alone. 3. The fall in urine creatinine excretion, and polyuria, after glycerol was reduced by γ-glutamyl l-dopa and the natriuresis abolished. 4. γ-Glutamyl l-dopa given alone caused a 4000-fold increase in urine dopamine excretion, associated with a natriuresis. 5. The administration of γ-glutamyl l-dopa reduces the severity of renal failure produced by glycerol.

scholarly journals Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure

2013 ◽  
Vol 304 (1) ◽  
pp. R10-R22 ◽  
Author(s):  
Martin Leduc ◽  
Xin Hou ◽  
David Hamel ◽  
Melanie Sanchez ◽  
Christiane Quiniou ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Artery ◽  
Artery Occlusion ◽  
Hek293 Cells ◽  
Heme Oxygenase 1 ◽  
Histological Changes ◽  
Ep4 Receptor ◽  
Renal Artery Occlusion

Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE2 is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP4 receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP4 receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE2-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP4-mediated relaxation of piglet saphenous vein rings, partially inhibited EP4-mediated cAMP production, but did not affect Gαi activation or β-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP4-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP4-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP4 receptor, resulting in improved renal function and integrity following acute renal failure.

Glomerular endothelin receptors during initiation and maintenance of ischemic acute renal failure in rats

1991 ◽  
Vol 260 (1) ◽  
pp. F110-F118
Author(s):  
B. M. Wilkes ◽  
A. R. Pearl ◽  
P. F. Mento ◽  
M. E. Maita ◽  
C. M. Macica ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Acid Treatment ◽  
Affinity Constant ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Receptor Sites ◽  
Sprague Dawley Rats ◽  
Receptor Number ◽  
Ischemic Acute Renal Failure

Glomerular endothelin (ET) receptors were studied in normal Sprague-Dawley rats and in rats with ischemic acute renal failure (ARF) induced by a 60-min occlusion of the left renal artery (right kidney intact). In normal rats ET bound to specific glomerular receptor sites [equilibrium affinity constant (Kd), 46.6 +/- 5.8 pM; receptor number (Ro), 1,167 +/- 160 fmol/mg (n = 7)]. ET infusion (90 ng.kg-1.min-1, intra-arterially) raised mean arterial pressure by 32 +/- 4 mmHg, lowered renal blood flow (RBF) by 62% and glomerular filtration rate (GFR) by 49%, and reduced the number of glomerular ET receptor sites by 62%. Reduced ET binding could not be explained by prior occupancy, because acid treatment (which dissociates bound ET from its receptors) did not increase receptor number. If elevated ET levels contributed to decreased RBF and GFR in ARF, glomerular ET receptors would be expected to down-regulate. In rats with ischemic ARF there were no differences in the number or affinity of glomerular ET receptors in the clamped or contralateral kidneys. Additional studies demonstrated that the downregulation response to ET infusion was intact in ARF. The data demonstrate that glomerular ET receptors are unaltered in ischemic ARF and do not support a role for increased glomerular ET in the alterations of renal hemodynamics in this model.

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