Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A growing body of evidence supports the notion that calcium antagonists exert a renal protective effect. Calcium antagonists may play an important future role in renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemia or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast media, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Such protection may extend to favorably influencing the course of chronic renal insufficiency, particularly when the latter is complicated by hypertension. Seven putative mechanisms have been proposed by which calcium antagonists may ameliorate the decline in GFR associated with renal insufficiency. These are: (a) reduction in blood pressure per se, (b) reduction in renal hypertrophy, (c) modulation of mesangial traffic of macromolecules, (d) reduction in metabolic activity in remnant renal tissue, (e) amelioration of uremic nephrocalcinosis, (f) reduction of pressure-induced calcium entry into vessel walls, and (g) reduction of free radical formation. Experimental investigations in rats with reduced renal mass, desoxycorticosterone-induced hypertension, or chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view.
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PMID:Calcium antagonists and renal protection. 851 90

The influence of ketanserin, a S2-serotonergic receptor blocker, on the impaired renal hemodynamics in a clamp model of renal ischemia in rats was investigated in this study. Serotonin-induced vasoconstriction of the renal vascular bed was augmented after ischemia. This constriction is blocked by ketanserin (0.05 mg/kg i.v. bolus, followed by 0.1 mg/kg per h infusion). The influence of the same ketanserin treatment on the response of RBF versus a stepwise lowering of the renal perfusion pressure was studied in post-ischemic kidneys with an established loss of autoregulation of RBF. An almost perfect restoration of the autoregulatory response was apparent after the S2-serotonergic antagonism. Despite this beneficial effect on renal hemodynamics, renal function, judged by measurement of GFR and urinary sodium excretion rate, was not influenced by an acute infusion of ketanserin in post-ischemic kidneys. It is suggested that serotonin plays a pivotal role in the suppression of autoregulation of RBF by a S2-serotonergic receptor-mediated vasoconstrictor effect in the post-ischemic kidney. It most likely masks the potential myogenic dilatory response of the smooth muscle cells in renal preglomerular microvasculature. Restoration of the renal autoregulatory capacity by S2-serotonergic receptor antagonism could be of clinical relevance in human post-ischemic acute renal failure.
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PMID:Beneficial influence of ketanserin on autoregulation of blood flow in post-ischemic kidneys. 872 97

Based on the previous demonstration of a renoprotective effect of arginine-glycine-aspartic acid (RGD) peptides in acute renal failure, experiments were designed to test the distribution and renal accumulation of the peptide. To accomplish this goal, in this study, RGD peptide was radiolabeled and its biodistribution and renal accumulation was determined in rats with ischemic acute renal failure (ARF). 99mTc-RGD with or without 111In-DTPA were injected intravenously in control and ARF rats. Various organs were dissected at different times after injection and subjected to gamma-scintillation counting and autoradiography (ARG). Blood clearance of 99mTc-RGD was rapid, with t1/2 < 10 min, and unchanged in ARF compared with control rats. Kidneys retained the largest portion of the injected dose in both control and ARF rats, as detected using scintillation counting and whole-body ARG (10.56 +/- 1.05% and 10.12 +/- 3.16% injected dose/g wet weight, respectively). Renal ARG revealed a significant increase in binding to the cortex in ARF kidneys, compared with that of control kidneys. Given the differences in renal blood flow and GFR in control and postischemic kidneys, the next series of experiments was performed with two radiopharmaceuticals, 99mTc-RGD and 111In-DTPA. The ratio of 99mTc-RGD:111In-DTPA was increased more than three-fold in ARF kidneys compared with control kidneys (2.7 +/- 0.15 versus 0.8 +/- 0.19, respectively). The results indicate that (1) RGD peptide undergoes a rapid clearance predominantly via the renal route; (2) despite a significant reduction in the renal perfusion, 99mTc-RGD peptide accumulates in the postischemic kidney; (3) this is consistent with the hypothesis on the involvement of RGD-recognizing integrins in the development of tubular obstruction in renal ischemia.
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PMID:Biodistribution and clearance of 99mTc-labeled Arg-Gly-Asp (RGD) peptide in rats with ischemic acute renal failure. 898 49

To clarify the role of nitric oxide (NO) in the pathogenesis of renovascular hypertension, we examined the effects of long-term oral administration of either the precursor substrate L-arginine or the NO synthesis inhibitor Nomega-nitro-L-arginine (L-NA) on systemic and renal hemodynamics in dogs with chronic two-kidney, one-clip (2K-1C) renovascular hypertension. Furthermore, the importance of NO in maintaining kidney function in chronic renal ischemia was evaluated. Chronic inhibition of NO production aggravated the rise in blood pressure (L-NA 117.7+/-6.8 vs. control 107.2 3.3 mmHg, p < 0.05 on day 1) and stimulated marked bradycardia (L-NA 84.9+/-3.2 vs. control 94.6+/-2.6 beats/min, p < 0.05 on day 1). These changes were associated with significant reductions in renal plasma flow (RPF, L-NA 0.03+/-0.02 vs. control 0.85+/-0.20 ml/min/kg, p < 0.01) and glomerular filtration rate (GFR, L-NA 0.02+/-0.01 vs. 0.22+/-0.05 ml/min/kg, p < 0.01) in the ischemic kidney. In contrast, in the contralateral non-clipped kidney, chronic inhibition of NO production induced a significant reduction in RPF with no significant change in GFR. Oral administration of L-arginine had no effect on the magnitude of hypertension. L-arginine significantly improved RPF (2.76+/-0.49 ml/min/kg) and GFR (0.61+/-0.08 ml/min/kg) in the ischemic kidney, whereas the elevation of RPF and GFR in the non-clipped kidney was not significant. Unilateral renal artery occlusion in these hypertensive dogs resulted in diffuse atrophic tubulointerstitial changes in the ischemic kidney. These changes were markedly aggravated by NO synthesis inhibition. On the other hand, L-arginine treatment significantly protected against the morphological changes of renal ischemia. These data show that NO plays a key role in the maintenance of renal function during the evolution of hypertension induced by chronic renal ischemia. In addition, these data demonstrate that renovascular hypertension is associated with a compensatory increase in the vasodilator function of the vascular endothelium.
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PMID:Role of nitric oxide in the evolution of renal ischemia in two-kidney, one-clip renovascular hypertension. 987 20

This study was undertaken to determine whether reactive oxygen species (ROS) are involved in the pathogenesis of ischemic acute renal failure (IARF) in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with combination of xanthine oxidase inhibitor (allopurinol), hydrogen peroxide scavenger (catalase), and hydroxyl radical scavenger (sodium benzoate). Serum creatinine level significantly increased 24 h after ischemia and remained higher to 72 h. Ischemia caused a reduction of GFR and an increase of FENa. Such changes were significantly attenuated by scavenger pretreatment. The uptake of p-aminohippurate in cortical slices and microsomal Na(+)-K(+)-ATPase activity were depressed in kidneys subjected to 72 h of reflow following ischemia, indicating impairment of tubular transport function, which were significantly attenuated by scavenger treatment. Renal blood flow 72 h after reflow was markedly reduced and it was restored by scavenger pretreatment. When animals were pretreated with a potent antioxidant DPPD, lipid peroxidation in cortex and medulla was significantly inhibited. However, ischemia-induced impairment of renal function was not attenuated by pretreatment of the antioxidant. These results suggest that radical scavengers may exert a protective effect against ischemia acute renal failure by other actions rather than ROS scavenging. Thus, the data do not support involvement of ROS in IARF in rabbits.
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PMID:Effects of radical scavengers and antioxidant on ischemic acute renal failure in rabbits. 1004 13

In 370 patients (pts) with hypertension(HT) in years 1986-1998 (168F + 202M, mean age 46 yrs) screening value of the following tests was evaluated: standard initial angioscintigraphy DTPA 99mTc(SA) in all pts(1-st screening group), significance of clinical suspicion on renovascular hypertension (RVHT) in the group of 74 pts (II-nd screening group). Captopril tests: renin captopril test(RCT) and isotopic captopril test (ICT) were performed in all 370 pts. Classical renal angiography as a reference test for renal artery stenosis (RAS) was performed in all pts suspected for RVHT on the basis of clinical anamnesis and or positive results of captopril tests. Results were as follows. Initial SA being abnormal in the whole group, appeared to be more significant for RAS only in the case of profound one side renal ischemia (GFR lower than 30% of total GFR). Resistance to three antihypertensive drugs, diastolic blood pressure > 120 mmHg and sudden onset of Ht, found in all 74 pts from the II-nd group, were the most significant clinical symptoms of RVHT, because critical RAS was found in 41, that is 55% of pts from the II-nd group. At least one positive CT was found in 37 from 42 pts with critical RAS in angiography with RTC being more sensitive and ICT more specific for hemodynamically significant RAS. The following screening protocol for RVHT was presented and discussed: precise clinical anamnesis followed by angiography or captopril tests according to the severity of clinical symptoms, aim of the study as well as accessibility and laboratory reproducibility of the captopril tests.
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PMID:[Screening for renovascular hypertension in own material (1986-1998)]. 1010 95

Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the interstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 +/- 17 mg/d treated, 229 +/- 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
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PMID:Contribution of angiotensin II to late renal injury after acute ischemia. 1086 84

The general use of bilateral rather than separate renal function evaluation has led to the publication of conflicting results concerning the effect of percutaneous transluminal renal angioplasty (PTRA) on renal function, especially in patients with atherosclerotic renal artery stenosis. The aim of this study was to evaluate prospectively, in standardized conditions, split renal function (SRF) and GFR outcome after successful PTRA, by measuring single kidney GFR with synchronous inulin or (51)Cr-ethylenediaminetetraacetic acid clearance and (99m)Tc-diethylenetriamine pentaacetic acid scintigraphy, in a well-defined population of patients with unilateral renal artery stenosis. Thirty-two consecutive hypertensive patients (18 with atherosclerotic and 14 with dysplastic disease) with significant unilateral stenosis of the main native renal artery (> or = 60%) and normal renal function were included in the study. Renal and angiographic follow-up evaluations were performed 6 mo after PTRA. PTRA alone or combined with stenting (n = 2) was technically successful in all patients. Repeat PTRA was necessary in two patients, evaluated 6 mo after the second PTRA. Six mo after PTRA, total GFR had increased slightly but significantly in the 29 patients with positive lateralization indices. SRF and single-kidney GFR of the stenotic kidney increased significantly, whereas concurrently the GFR and SRF of the nonstenotic kidney decreased significantly. Six mo after successful PTRA reducing renal ischemia, a reversal of both the hypoperfusion of the stenotic side and the hyperperfusion of the nonstenotic side was observed, which was accompanied by a slight increase in total GFR.
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PMID:Split renal function outcome after renal angioplasty in patients with unilateral renal artery stenosis. 1137 47

Previous studies have demonstrated that levels of tumor necrosis factor-alpha (TNF-alpha) or its mRNA expression are increased in acute renal failure of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-alpha production, provides a protective effect against ischemic acute renal failure in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with PTX (30 mg/kg, i.v.) 10 min before release of clamp. At 24 h of reperfusion of blood after ischemia, changes in renal function, renal blood flow, and the expression of TNF-alpha mRNA were evaluated. Ischemia/reperfusion caused a marked reduction in GFR, which was accompanied by an increase of serum creatinine levels. Such changes were significantly attenuated by PTX pretreatment. PTX ameliorated the impairment of renal tubular function, but it had no effect on the reduction of renal blood flow induced by ischemia/reperfusion. The protective effect of PTX on functional changes was supported by morphological studies. The impairment of glucose and phosphate reabsorption in postischemic kidneys was associated with a depression in the expression of Na+-glucose and Na+-Pi transporters. The expression of TNF-alpha mRNA was increased after reperfusion, which was inhibited by PTX pretreatment. The PTX pretreatment in vitro prevented the release of lactate dehydrogenase induced by an oxidant t-butylhydroperoxide in rabbit renal cortical slices, but it did not produce any effect on the oxidant-induced lipid peroxidation, suggesting that PTX protection is not resulted from its antioxidant action. These results suggest that PTX may exert a protective effect against ischemic acute renal failure by inhibiting the production of TNF-alpha in rabbits.
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PMID:Effect of pentoxifylline on ischemic acute renal failure in rabbits. 1177 15

The role of nitric oxide (NO) and prostaglandins (PG) in modifying renal hemodynamics was examined in clipped and nonclipped kidneys of unilateral renal artery stenosis. Chronic unilateral renal ischemia was established by 4-wk-clipping the left renal artery of canine kidneys, and renal interstitial nitrate+nitrite and PGE(2) contents were evaluated by the microdialysis technique. Unilateral renal artery stenosis caused 45 +/- 1 and 73 +/- 1% decrements in renal plasma flow (RPF) in moderately and severely clipped kidneys and 21 +/- 3% decrements in nonclipped kidneys with severe stenosis. Renal nitrate+nitrite decreased in moderately (-31 +/- 1%) and severely clipped kidneys (-63 +/- 4%). N(omega)-nitro-L-arginine methyl ester reduced RPF (-56 +/- 3%) and glomerular filtration rate (GFR; -54 +/- 3%) in moderately clipped kidneys, whereas this inhibitory effect was abolished in severely clipped kidneys. In contrast, renal PGE(2) contents increased modestly in moderate clipping and were markedly elevated in severely clipped kidneys (from 111 +/- 7 to 377 +/- 22 pg/ml); sulpyrine impaired renal hemodynamics only in severely clipped kidneys. In contralateral nonclipped kidneys, although renal PGE(2) was not increased, sulpyrine reduced RPF (-32 +/- 1%) and GFR (-33 +/- 3%) in severe stenosis. Collectively, NO plays a substantial role in maintaining renal hemodynamics both under basal condition and in moderate renal artery stenosis, whereas the contributory role shifts from NO to PG as renal artery stenosis progresses. Furthermore, because intrarenal angiotensin II is reported to increase in nonclipped kidneys, unilateral severe ischemia may render the nonclipped kidney susceptible to PG inhibition.
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PMID:Stenosis-dependent role of nitric oxide and prostaglandins in chronic renal ischemia. 1193 96


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