Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.
 ...
PMID:Prostaglandins and the kidney. 33 46

The effects of complete ischemia on cerebral arachidonic acid (AA) metabolism were investigated in the isolated perfused rat brain. During 12.5 min of ischemia, AA, 5-hydroxy-6,8,11,14-eicosatetraenoic acid, and 15-hydroxy-5,8,11,13-eicosatetraenoic acid increased 129-, 4-, and 10-fold, respectively, while subsequent reperfusion for 30 min resulted in normalized levels independently of the duration of preceding ischemia. Prostaglandin (PG) F2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and thromboxane (Tx) B2 remained at preischemic levels during 12.5 min of complete ischemia. However, at the end of subsequent reperfusion for 30 min, the levels of the prostanoids PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and TxB2 increased according to the preceding ischemic time. The levels reached a maximum after 7.5 min of ischemia and were elevated by 7-, 14-, 48-, 3-, and 30-fold, respectively. A prolongation of ischemia of up to 12.5 min was not associated with further increases of prostanoids at the end of reperfusion. The mechanisms underlying the metabolism of eicosanoids are discussed in relation to the changes of cortical direct current potential.
 ...
PMID:Eicosanoids in rat brain during ischemia and reperfusion--correlation to DC depolarization. 232 22

Platelets are suggested to exacerbate ischemia-induced myocardial injury, which has led to the study of various antiplatelet therapies including thromboxane synthetase inhibitors (TXSI). Two such agents, benzylimidazole and OKY-046, reduce infarct size commensurate with a diminution in serum thromboxane B2 formation in anesthetized dogs subjected to 90 minutes of coronary artery occlusion followed by 5 hours of reperfusion. In contrast, platelet depletion with specific antiserum does not reduce infarct size but prevents the cardioprotection afforded by the TXSI. Platelet-derived prostaglandin endoperoxides (PGG2 and PGH2), which cannot be converted to thromboxane A2 in the inhibited platelet, can be transformed to PGE2 and PGD2 in plasma and to PGI2 by the blood vessel wall. These prostaglandins are considered "cardioprotective." Consequently, a low dose of aspirin (3-5 mg/kg) given 24 hours before coronary occlusion was used to selectively block the platelet cyclooxygenase enzyme. Aspirin, by itself, does not reduce infarct size, but it suppresses the myocardial salvage induced by OKY-046. Thus, TXSI reduce infarct size by platelet-dependent, aspirin-sensitive mechanism that depends on the redirection of platelet-derived PGG2 and PGH2 to protective metabolites, rather than inhibition of thromboxane A2 per se. Moreover, myocardial salvage induced by the TXSI is accompanied by a reduction in neutrophil accumulation in the myocardium, as indicated by the levels of the neutrophil-specific myeloperoxidase enzyme. Platelet depletion or pretreatment with aspirin prevents the TXSI-induced suppression of neutrophil accumulation. Consequently, it is proposed that the prostaglandin-mediated protective effects of TXSI can be resolved, at least in part, in terms of a braking action on neutrophil activation to prevent leukocyte-dependent tissue injury.
 ...
PMID:Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. 312 73

Clinical studies have demonstrated elevated levels of both arachidonic acid and prostaglandins in the cerebrospinal fluid of humans after ischemic stroke and subarachnoid hemorrhage. Such increases in free fatty acid, arachidonic acid, and prostaglandin concentrations suggest excessive production and accumulation of these substances in the ischemic brain. We used a rabbit model of ischemic infarction to examine the relation between controlled central nervous system ischemia and cerebrospinal fluid prostaglandin levels. We found that following stroke PGF2 alpha and not PGD2 was the predominant prostaglandin present in the cerebrospinal fluid. PGF2 alpha also underwent the largest percent increase over control prostaglandin concentrations. This is similar to human and dog cerebrospinal fluid studies, which demonstrate PGF2 alpha as the predominant prostaglandin following ischemic injury. The lack of PGD2 elevation under ischemic conditions may suggest that the rabbit model is more like stroke in humans than the rat or gerbil models. Our preliminary work demonstrates that it is practical to study postischemic prostaglandin changes in cerebrospinal fluid rather than in brain tissue in a rabbit model of central nervous system ischemia.
 ...
PMID:Prostaglandin concentrations in cerebrospinal fluid of rabbits under normal and ischemic conditions. 335 21

We found recently that exogenously administered PGD2, PGE1 and PGI2 showed a protective effect against cerebral hypoxia/ischemia in mice. In the present study, to find out whether these PGs play a pathophysiological role in cerebral hypoxia/ischemia, we examined a possible role of PGs in the development of adaptive protection against cerebral hypoxia/ischemia. Mice were pretreated with a sublethal dose of KCN, hypoxic gas mixture and electroshock 10-120 min before tests. Ten to thirty min after pretreatment with a sublethal dose of KCN, mice proved to be significantly protected against cerebral hypoxia/anoxia in all models studied: KCN-induced anoxia, normobaric hypoxia and decapitation-induced gasping. Similar results were observed when hypoxic gas and electroshock were used as pretreatments. These facts indicate that the protective effect does not depend on how cerebral hypoxia/anoxia is induced but on the substances formed in the brain after hypoxia/anoxia as well as electroshock. Brain concentrations of cyclooxygenase products markedly increased subsequent to hypoxia/anoxia as well as electroshock. The increase in PGs formation as well as resistance to hypoxia was prevented by pretreatment with indomethacin. These findings suggest that endogenously formed PGs at least including the three PGs, PGD2, PGE1 and prostacyclin in mouse brain during or after hypoxia/ischemia are responsible for the increase of resistance to hypoxia/ischemia.
 ...
PMID:A possible role of endogenously formed cerebral prostaglandins in the development of adaptive protection against cerebral hypoxia/ischemia in mice. 344 51

The postischemic production of PGE2, PGD2, 6-keto-PGF1 alpha, and TXB2 in brain tissue was studied in Mongolian gerbils using tissue extraction as well as a new ex vivo method. This new method permits the study of prostaglandin synthesis in slices from discrete areas of the brain (cortex, hippocampus, striatum, hypothalamus). Gerbils were sacrificed at 0, 5, and 30 minutes, and 4 and 24 hours after a 15-minute occlusion of both carotid arteries. Apart from 6-keto-PGF1 alpha, tissue prostaglandins determined by the extraction method were significantly increased 3 and 30 minutes after reperfusion. The most pronounced changes found by the ex vivo method were increased productions of PGD2 immediately after reperfusion (285% in cortex, 215% in hypothalamus) and PGE2 (350% in hippocampus, 320% in striatum) 4 hours after reperfusion. At 24 hours after reperfusion PGE2 and PGD2 synthesis were significantly decreased by 23-70% of the values obtained from sham-operated controls. Thromboxane increased slightly in all areas after recirculation and subsequently decreased to values below the control level in striatum. The results obtained by ex vivo incubation of tissue slices demonstrate that ischemia and subsequent recirculation cause site-, time-, and PG-specific changes of tissue eicosanoid production.
 ...
PMID:Postischemic production of eicosanoids in gerbil brain. 346 70

Ischemia was induced for 25 min in the spinal cord of rabbits followed by a long term period of recirculation. At various time points of recirculation (5, 30 min, 4, 18 hr and 1 wk) slices were taken from the ischemic region and incubated for 45 min in Krebs-Ringer solution. The levels of the eicosanoids, PGE2, PGD2, PGF2 alpha, TXB2, 6-keto-PGF1 alpha and 5-HETE accumulated in the incubation medium were measured by radioimmunoassay. TXB2, release was found to be increased at an early (5 min) and late (1 wk) period of reperfusion. A seven-fold increase in the release of 5-HETE was found 5 min after reperfusion that tended to stay elevated at 18 hr and 1 week of recirculation. PGI2 synthetase activity decreased by 40% at 30 min, with return to normal at later time points. The ratio of TXA2/PGI2 was significantly higher than control at 30 min and 1 wk. The synthesis of PGE2, PGD2 and PGF2 alpha was maintained at normal levels throughout the complete course of reperfusion. No changes in eicosanoid synthesis were noted in remote spinal cord regions. The significant increase of TXA2 synthesis at 5 min and 1 wk of reperfusion may point to a role of this arachidonate metabolite in the acute events and in the later stages of neurological dysfunction. The enhanced release of 5-HETE, a metabolite of 5-HETE, suggest an enhanced formation of leukotriene B4 and peptide leukotrienes and a potential role for these 5-lipoxygerase metabolites of arachidonate in ischemia injury to the brain and the spinal cord.
 ...
PMID:Increased thromboxane A2 and 5-HETE production following spinal cord ischemia in the rabbit. 347 67

Using the rat middle cerebral artery occlusion model, alterations in the eicosanoid synthetic capacity of brain microvessels following ischemia were studied by radiochromatography. Brain microvessels of normal rats predominantly produced hydroxyacids with relatively small amounts of PGD2 and PGE2 from exogenous arachidonic acid. Confirmation that hydroxyacids and prostaglandins were products respectively of lipoxygenase(s) and cyclooxygenase was obtained by experiments using indomethacin and eicosatetraynoic acid. The eicosanoid synthetic capacity of the brain microvessel, especially of hydroxyacids, was significantly enhanced 24 and 72 hours after the onset of ischemia. Because this is the phase of maximum edema in the present model, enhanced eicosanoid production in the brain microvessel may be involved in the mechanisms that underly ischemic brain edema.
 ...
PMID:Ischemic brain edema following occlusion of the middle cerebral artery in the rat. II: Alteration of the eicosanoid synthesis profile of brain microvessels. 396 53

Several of the cyclooxygenase products of arachidonic acid were measured in the cerebral hemispheres of gerbils subjected to transient interruption of the cerebral circulation. The levels of PGD2, PGF2 alpha, PGE2, TXB2, 13, 14-H2-15-keto-PGE2, and the stable nonenzymic product of prostacyclin, 6-keto-PGF1 alpha, were not altered at the end of a 5-min period of ischemia. However, the onset of reperfusion was accompanied by a rapid accumulation of these products. Levels were highest during the initial period of reperfusion, then decreased to approach control levels after 120 min. PGD2, PGF2 alpha, and PGE2 were the predominant metabolites detected. This postischemic accumulation of arachidonic acid metabolites could be blocked by prior administration of inhibitors of cyclooxygenase activity.
 ...
PMID:Accumulation of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion. 677 64

Prostaglandin E1,PGD2, and 16,16 dimethyl prostaglandin E2 were studied in an isolated perfused cat heart preparation during normal conditions and in myocardial ischemia. Under ischemic perfusion, prostaglandin E1 showed some protective action on the release of creatine kinase into perfusate during ischemia, but none of the prostaglandins studied prevented increases in perfusate creatine kinase after reperfusion. Prostaglandin E1 also showed significant membrane stabilizing activity reducing the rate of lysosomal hydrolase release from cat liver lysosomes. Prostaglandin E1 may be beneficial in myocardial ischemia due to its membrane stabilizing action and perhaps to other effects but it did not exert significant protective effects on reperfusion injury of the ischemic myocardium under conditions of these experiments.
 ...
PMID:Cardiac effects of prostaglandins during global ischemia in isolated perfused cat hearts. 695 73


1 2 3 Next >>