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)

To test the possibility that adenosine may be involved in a urine concentrating mechanism, effects of 1-phenylisopropyladenosine (PIA) on cyclic AMP levels have been examined in medullary thick ascending limb (mTAL) and medullary collecting duct (MCD) isolated from the rat. Low and high doses of PIA did not alter basal cyclic AMP levels in both segments. However, PIA depressed vasopressin-dependent cyclic AMP production in MCD in a dose-dependent manner: this effect of PIA was maximum at 10(-6) M. 8-Phenyltheophylline, a competitive inhibitor for adenosine receptor, completely abolished this inhibitory effect of PIA. This finding may suggest an existence of adenosine receptor on the MCD. In mTAL, PIA also suppressed vasopressin-mediated cyclic AMP generation. The present study shows an interaction between PIA and vasopressin in both MCD and mTAL. This interaction may contribute in part to urinary-concentrating disturbance in renal ischemia.
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PMID:Effect of phenylisopropyladenosine on vasopressin-dependent cyclic AMP generation in defined nephron segments from rat. 282 7

Brief renal ischemia-reperfusion is reported to precondition the myocardium; however, the underlying mechanisms are unknown. This phenomenon was, therefore, investigated using an in vivo rabbit model of acute myocardial infarction. Characterization of the mechanisms involved was performed using the nonselective adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-SPT) and the ATP-sensitive potassium (KATP) channel blocker sodium 5-hydroxydecanoate (5-HD). Pentobarbital-anesthetized rabbits underwent a left thoracotomy and pericardiotomy. A laparotomy was then performed to expose the left renal artery. Animals were either preconditioned with a 10-min occlusion of the renal artery followed by 10 min of reperfusion or underwent a 20-min sham period of anesthesia. Subsequently, the left coronary artery was then occluded for 30 min and reperfused for 2 h. Infarct-to-risk ratio was limited from 32.7 +/- 4.0% (n = 12) in controls to 17.8 +/- 3.0% (n = 9; P = 0.002) in preconditioned hearts. Protection was abolished by 7.5 mg/kg iv 8-SPT (36.7 +/- 3.7%; n = 6) or 5 mg/kg iv 5-HD (33.1 +/- 4. 4%; n = 6) administered before preconditioning. 8-SPT (40.0 +/- 4. 4%; n = 6) or 5-HD (40.5 +/- 4.2%; n = 6) did not affect infarct-to-risk ratio in sham controls. Thus activation of both adenosine receptors and KATP channels appears to be involved in acute renal preconditioning of the myocardium.
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PMID:Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. 981 59

Renal ischemia and reperfusion during aortic and renal transplant surgery result in ischemic-reperfusion injury. Ischemic preconditioning and adenosine infusion before ischemia protect against ischemic-reperfusion injury in cardiac and skeletal muscle, but these protective phenomena have not been demonstrated in the kidney. Rats were randomized to sham operation, 45-min renal ischemia, ischemic preconditioning with four cycles of 8-min renal ischemia and 5-min reperfusion followed by 45-min renal ischemia, systemic adenosine pretreatment before 45-min renal ischemia, or pretreatments with selective adenosine receptor subtype agonists or antagonists before 45-min renal ischemia. Forty-five minutes of renal ischemia followed by 24 h of reperfusion resulted in marked rises in blood urea nitrogen and creatinine. Ischemic preconditioning and adenosine pretreatment protected renal function and improved renal morphology. A(1) adenosine receptor activation mimics and A(1) adenosine antagonism blocks adenosine-induced protection. In addition, A(3) adenosine receptor activation before renal ischemia worsens renal ischemic-reperfusion injury, and A(3) adenosine receptor antagonism protects renal function. We demonstrate for the first time that rat kidneys can be preconditioned to attenuate ischemic-reperfusion injury and adenosine infusion before ischemic insult protects renal function via A(1) adenosine receptor activation. Our data suggest that an A(1) adenosine agonist and A(3) adenosine antagonist may have clinically beneficial implications where renal ischemia is unavoidable.
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PMID:Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A(1) and A(3) receptors. 1071 May 42

The effects of renal ischemic preconditioning (RIP) on ischemia-reperfused myocardium were examined in the urethane-anesthetized rabbit to determine whether RIP may provide cardioprotection and to observe the role of the renal nerve in such condition. The results obtained are as follows: (1) During 45 min myocardial ischemia and subsequent 180 min reperfusion, blood pressure, heart rate and myocardial oxygen consumption decreased progressively. Epicardial electrographic ST-segment was elevated significantly in the period of ischemia and returned to the baseline gradually in the course of reperfusion. The myocardial infarct size occupied 55.80 +/- 1.25% of the area at risk. (2) RIP significantly reduced the myocardial infarct size to 36.51 +/- 2.80% (P < 0.01), indicating the cardioprotective effect of such an intervention. (3) Renal nerve section (RNS) completely abolished the cardioprotection afforded by RIP, though RNS per se did not affect the myocardial infarct size produced by ischemia-reperfusion. (4) During 10 min renal ischemia, the averaged multi-unit discharge rate of the renal afferent was increased from 0.14 +/- 0.08 to 0.65 +/- 0.12 imp/s (P < 0.01). (5) Pretreatment with an adenosine receptor antagonist 8-phenyltheophylline (10 mg/kg) markedly attenuated the discharge rate of the renal afferent induced by transient renal ischemia, implying that adenosine released in ischemic kidney activated the renal afferent. It is suggested that activation of renal afferents by transient renal ischemia-reperfusion plays an important role in the cardioprotection afforded by RIP.
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PMID:Role of renal nerve in cardioprotection provided by renal ischemic preconditioning in anesthetized rabbits. 1135 2

Ischemia and reperfusion during renal transplant and aortic surgery result in renal ischemic-reperfusion injury. Previously, we showed that preischemic adenosine treatment protects renal function via A(1) adenosine receptor (AR) activation. In contrast, in the cardiac and pulmonary systems, postischemic adenosine has potent anti-inflammatory attributes and is protective against reperfusion injury via activation of A(2a) ARs. We questioned whether adenosine given after an ischemic insult protects renal function in rats, and we sought to determine the AR subtype and intracellular second messengers involved. Rats were randomized to a sham operation, 45 minutes of renal ischemia and reperfusion and treatments with systemic adenosine or selective AR agonists and antagonists, or treatments of dibutyryl cyclic adenosine monophosphate (cAMP) after 45 minutes of renal ischemia but before reperfusion. Forty-five minutes of renal ischemia followed by 24 hours of reperfusion led to severe renal dysfunction as indicated by marked rises in creatinine and histologically evident renal tubular damage. Adenosine treatment after ischemia protected renal function and improved tubular histology. This protection was mediated via A(2a) AR activation because the A(2a)-selective AR agonist [4-((N-ethyl-5'-carbamoyadenos-2-yl)-aminoethyl)-phenylpropionic acid (CGS-21680)] mimics adenosine-induced renal protection, and the A(2a)-selective AR antagonist [8-(3-chlorostyryl)caffeine (CSC)] blocks adenosine-induced renal protection. A(1) or A(3) AR agonists and antagonists did not mimic and block adenosine-induced renal protection. The signaling intermediates of A(2a) AR-mediated renal protection appear to include cAMP because dibutyryl cAMP mimicked adenosine and CGS-21680 mediated renal protection. Rat kidneys can be protected against reperfusion injury via postischemic A(2a) AR activation or cAMP. These data suggest that A(2a) adenosine agonists may have clinically beneficial implications when renal ischemia is unavoidable.
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PMID:Systemic adenosine given after ischemia protects renal function via A(2a) adenosine receptor activation. 1153 95

The effects of renal ischemia on spontaneous electrical activity and Fos protein expression of nucleus paragigantocellularis lateralis (PGL) in rostral ventrolateral medulla (RVLM) were observed in 67 anesthetized Sprague-Dawley rats with sinoaortic denervation by using extracellular recording and immunohistochemical techniques. The results obtained are as follows. (1) Renal ischemia increased the discharge rate from 11.40 +/- 1.08 to 21.1 +/- 1.74 spikes/s (P < 0.001) in 28 out of 30 PGL neurons, while blood pressure and heart rate had no significant change (P > 0.05). (2) Administration of 8-phenyltheophylline (8-PT), an adenosine receptor antagonist, did not affect the discharge rate of PGL neurons, but could partially inhibit the effects of renal ischemia in 17 units (P < 0.05). (3) Renal ischemia resulted in a remarkable increase in the number of Fos-like protein immunoreactive PGL neurons in the RVLM (P < 0.01). (4) Fos protein expression induced by renal ischemia was significantly inhibited by pretreatment with 8-PT (P < 0.05). Taken together, it is concluded that renal ischemia induces an increase in spontaneous electrical activity and Fos protein expression in PGL neurons of RVLM, and that adenosine released within ischemic kidney may be involved in such effects.
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PMID:Renal ischemia enhances electrical activity and Fos protein expression of the rostral ventrolateral medullary neurons in rats. 1183 21

The present study was undertaken to define whether the renal artery occlusion (RAO) would activate the catecholaminergic neurons in the brainstem nuclei by double immunohistochemical method for detecting Fos and tyrosine hydroxylase. The results are as follows: (1) while the basal expression of Fos was relatively low in the brainstem, RAO was capable of inducing a robust Fos-like immunoreactive neurons in the nucleus tractus solitarius (NTS), area postrema (AP), nucleus paragigantocellularis lateralis (PGL) and locus coeruleus (LC); (2) numerous catecholaminergic neurons in NTS, AP, PGL and LC could be activated by RAO as shown by Fos expression; and (3) these responses to RAO were significantly attenuated by pretreatment with an adenosine receptor antagonist 8-phenyltheophylline. The results suggest that RAO can activate a large number of neurons including some catecholaminergic neurons in the brainstem nuclei. Such effects of renal ischemia may be attributed to RAO-induced adenosine release from the kidney which subsequently activates renal afferents.
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PMID:Renal ischemia-induced Fos expression in catecholaminergic neurons of rats. 1193 Feb 23

A(3) adenosine receptor (AR) activation and inhibition worsen and improve, respectively, renal function after ischemia-reperfusion (I/R) injury in rats. We sought to further characterize the role of A(3) ARs in modulating renal function after either I/R or myoglobinuric renal injury. A(3) knockout mice had significantly lower plasma creatinines compared with C57 controls 24 h after I/R or myoglobinuric renal injury. C57 control mice pretreated with the A(3) AR antagonist [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5 dicarboxylate] or agonist [0.125 mg/kg N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (IB-MECA)] demonstrated improved or worsened renal function, respectively, after I/R or myoglobinuric renal injury. Higher doses of IB-MECA were lethal in C57 mice subjected to renal ischemia. H(1) but not H(2) histamine receptor antagonist prevented death in mice pretreated with IB-MECA before renal ischemia. Improvement in renal function was associated with significantly improved renal histology. In conclusion, preischemic A(3) AR activation (0.125 mg/kg IB-MECA) exacerbated renal I/R injury in mice. Mice lacking A(3) ARs or blocking A(3) ARs in wild-type mice resulted in significant renal protection from ischemic or myoglobinuric renal failure.
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PMID:A3 adenosine receptor knockout mice are protected against ischemia- and myoglobinuria-induced renal failure. 1238 99

It was previously demonstrated that preischemic A(1) adenosine receptor (AR) activation protects renal function after ischemia-reperfusion (IR) injury in rats. The role of the A(1) AR in modulating inflammation, necrosis, and apoptosis in the kidney after IR renal injury was further characterized. C57BL/6 mice were subjected to 30 min of renal ischemia, with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine or 2- chlorocyclopentyladenosine (selective A(1) AR antagonist and agonist, respectively). Plasma creatinine levels and renal inflammation, necrosis, and apoptosis were compared 24 h after renal injury. C57BL/6 mice that had been pretreated with the A(1) AR agonist demonstrated significantly improved renal function and reduced expression of inflammatory markers, necrosis, and apoptosis 24 h after IR injury. In contrast, C57BL/6 mice that had been pretreated with the A(1) AR antagonist demonstrated significantly worsened renal function and increased expression of inflammatory markers, necrosis, and apoptosis. In conclusion, it was demonstrated that endogenous and exogenous preischemic activation of the A(1) AR protects against IR injury in vivo, through mechanisms that reduce inflammation, necrosis, and apoptosis.
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PMID:A1 adenosine receptor activation inhibits inflammation, necrosis, and apoptosis after renal ischemia-reperfusion injury in mice. 1469 62

A(2A) adenosine receptor (A(2A)R)-expressing bone marrow (BM)-derived cells contribute to the renal protective effect of A(2A) agonists in renal ischemia-reperfusion injury (IRI). We performed IRI in mice lacking T and B cells to determine whether A(2A)R expressed in CD4+ cells mediate protection from IRI. Rag-1 knockout (KO) mice were protected in comparison to wild-type (WT) mice when subjected to IRI. ATL146e, a selective A(2A) agonist, did not confer additional protection. IFN-gamma is an important early signal in IRI and is thought to contribute to reperfusion injury. Because IFN-gamma is produced by kidney cells and T cells we performed IRI in BM chimeras in which the BM of WT mice was reconstituted with BM from IFN-gamma KO mice (IFN-gamma KO-->WT chimera). We observed marked reduction in IRI in comparison to WT-->WT chimeras providing additional indirect support for the role of T cells. To confirm the role of CD4+ A(2A)R in mediating protection from IRI, Rag-1 KO mice were subjected to ischemia-reperfusion. The protection observed in Rag-1 KO mice was reversed in Rag-1 KO mice that were adoptively transferred WT CD4+ cells (WT CD4+-->Rag-1 KO) or A(2A) KO CD4+ cells (A(2A) KO CD4+-->Rag-1 KO). ATL146e reduced injury in WT CD4+-->Rag-1 KO mice but not in A(2A) KO CD4+-->Rag-1 KO mice. Rag-1 KO mice reconstituted with CD4+ cells derived from IFN-gamma KO mice (IFN-gamma CD4+-->Rag-1 KO) were protected from IRI; ATL146e conferred no additional protection. These studies demonstrate that CD4+ IFN-gamma contributes to IRI and that A(2A) agonists mediate protection from IRI through action on CD4+ cells.
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PMID:Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-gamma. 1649 70


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