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

Both the isolated perfused rabbit heart and kidney are capable of synthesizing prostaglandin (PG) I(2). The evidence that supports this finding includes: (a) radiochemical identification of the stable end-product of PGI(2), 6-keto-PGF(1alpha), in the venous effluent after arachidonic acid administration; (b) biological identification of the labile product in the venous effluents which causes relaxation of the bovine coronary artery assay tissue and inhibition of platelet aggregation; and (c) confirmation that arachidonic acid and its endoperoxide PGH(2), but not dihomo-gamma-linolenic acid and its endoperoxide PGH(1), serve as the precursor for the coronary vasodilator and the inhibitor of platelet aggregation. The rabbit heart and kidney are both capable of converting exogenous arachidonate into PGI(2) but the normal perfused rabbit kidney apparently primarily converts endogenous arachidonate (e.g., generated by stimulation with bradykinin, angiotensin, ATP, or ischemia) into PGE(2); while the heart converts endogenous arachidonate primarily into PGI(2). Indomethacin inhibition of the cyclo-oxygenase unmasks the continuous basal synthesis of PGI(2) by the heart, and of PGE(2) by the kidney. Cardiac PGI(2) administration causes a sharp transient reduction in coronary perfusion pressure, whereas the intracardiac injection of the PGH(2) causes an increase in coronary resistance without apparent cardiac conversion to PGI(2). The perfused heart rapidly degrades most of the exogenous endoperoxide probably into PGE(2), while exogenous PGI(2) traverses the heart without being metabolized. The coronary vasoconstriction produced by PGH(2) in the normal perfused rabbit heart suggests that the endoperoxide did not reach the PGI(2) synthetase, whereas the more lipid soluble precursor arachidonic acid (exogenous or endogenous) penetrated to the cyclooxygenase, which apparently is tightly coupled to the PGI(2) synthetase.
 ...
PMID:Cardiac and renal prostaglandin I2. Biosynthesis and biological effects in isolated perfused rabbit tissues. 34 5

In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.
 ...
PMID:The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver. 128 66

Fluorocarbon emulsions are presently being developed to serve as injectable oxygen carriers (so-called "blood substitutes"). In this approach oxygen is simply dissolved in the liquid carrier and the amount of gas dissolved is proportional to its partial pressure. Increasing the O2-delivering capacity is therefore achieved more easily by increasing the oxygen content of the air breathed by the patient than by increasing the dose of fluorocarbon administered. The absence of a chemical bond between the gas and its carriers allows over 90% of the transported oxygen to be delivered. The fluorocarbon droplets act as oxygen carriers , and also appear to facilitate its diffusion. Chemically and biologically highly inert, fluorocarbons are excreted by exhalation without being metabolized. The first generation of emulsions, exemplified by Fluosol has only limited efficacy due to its low fluorocarbon content, low intravascular persistence and insufficient stability. It has to be stored and distributed frozen, then reconstituted prior to use. Fluosol has nevertheless been licensed by the Food and Drug Administration for use during high risk PTCA. The second generation of injectable fluorocarbon emulsions, exemplified by Oxygent is 4-5 times more concentrated and consequently more efficacious than Fluosol. Considerably more stable, this emulsion can be stored for over one year at 5-8 degrees C and is ready for use. The fluorocarbon used has a significantly shorter organ-retention time. The applications of the present emulsions are still limited by their short intravascular persistence, and are those for which prolonged efficacy is not required, which includes perioperative hemodilution, ischemia, cardioplegia, reperfusion, sensitization of tumors to radio- and chemotherapy, organ preservation and diagnosis. The efficacy of the new emulsions has been established in various animal models. The mild side-effects observed in Phase I clinical trials appear to result from a transient activation of the monocyte/macrophage system and to be suppressed prophylactically by cyclooxygenase inhibitors or corticosteroids. Research is presently oriented towards controlling intravascular persistence better, increasing emulsion stability further, minimizing side-effects and optimizing emulsion characteristics for specific indications.
 ...
PMID:[Fluorocarbon emulsions as injectable oxygen carriers. Recent progress and perspectives]. 128 38

Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) are the metabolites of arachidonic acid (AA) that increase in forebrain following global ischemia and reperfusion. These mediators are highly potent vasoconstrictors of cerebral arteries leading to enhanced vascular permeability that induces the formation of vasogenic edema. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of PGE2 and LTC4 produced in the forebrain were measured and the effects of these mediators in short duration and prolonged reperfusion were investigated and then correlated with neuropathological findings. We found statistically significant reduction both in PGE2 and LTC4-like activities after just 10 min ischemia (p less than 0.05, p less than 0.05). PGE2-like activity significantly increased in the 4th and 60th min of reperfusion (p less than 0.05, p less than 0.05). In the 15th min of reperfusion, PGE2 was found to be significantly reduced (p less than 0.005) that may be due to the formation of free oxygen radicals by activation of PG hydroperoxidase reaction that inhibits PGE2 production in the cyclooxygenase pathway. LTs were not significantly increased in any reperfused group. Inhibition of the lipoxygenase pathway of AA metabolism may occur as a result of 15-HPETE (15-hydroperoxyeicosatetraenoic acid) production. Pathologically, edema and degeneration of brain tissue were seen beginning from the 4th min of reperfusion that reached a peak in the 60th min of reperfusion which is in accordance with biochemical changes in the damaged tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prostaglandin E2 and leukotriene C4 levels following different reperfusion periods in rat brain correlated with morphological changes. 140 66

Acetylcholine (ACh) and nitroglycerin (NTG) were used as probes to study endothelium-dependent and endothelium-independent vascular relaxation in isolated perfused transverse paraumbilical human skin flaps. It was observed that ACh (10(-6) M) significantly (p < 0.05) decreased the vascular resistance and increased dermal capillary perfusion (assessed by surface fluorometry) in norepinephrine (NE, 10(-6) M) preconstricted skin flaps, despite the presence of a cyclooxygenase inhibitor (indomethacin, 3 x 10(-5) M) and a beta-adrenergic receptor antagonist (propranolol, 10(-6) M). The ability of ACh to induce vascular relaxation in NE-preconstricted skin flaps was lost after damaging the vascular endothelial lining with saponin perfusion (100 mg.L-1, 5 min). In contrast, NTG (10(-6) M) induced vascular relaxation to a similar extent before and after saponin treatment. In a separate study, ACh was seen to induce vascular relaxation in a concentration-dependent manner in skin flaps preconstricted with NE (10(-6) M). This vascular relaxation effect of ACh over the dose range of 10(-9)-10(-5) M was significantly (p < 0.01) inhibited in the presence of N omega-nitro-L-arginine (10(-5) M), a nitric oxide (NO) synthesis inhibitor. These observations were taken to indicate the presence of endothelium-dependent and endothelium-independent vascular relaxation in human skin flaps and that the ACh-induced endothelium-dependent relaxation is probably mediated by NO. The importance of impairment of endothelium-dependent relaxation in the pathogenesis of skin flap ischemia, and the potential use of topical nitrovasodilators or NO donors for prevention and (or) treatment of skin flap ischemia were also discussed.
 ...
PMID:Evidence for endothelium-dependent and endothelium-independent vasodilation in human skin flaps. 149 89

The mechanism whereby preconditioning with a transient period of ischemia renders the heart resistant to infarction from a subsequent ischemic insult is unknown. The purpose of this study was to determine whether cyclooxygenase pathways are involved in preconditioning's protection. Two inhibitors of that pathway, meclofenamate (MEC) and aspirin (ASP), were test in an in situ and a blood perfused isolated heart model, respectively. Preconditioning was achieved with 5 minute ischemia and 10 minutes reperfusion. All in situ hearts underwent 30 minute ischemia followed by 180 minute reperfusion, while the isolated hearts experienced 45 minute ischemia plus 120 minute reperfusion. Infarct size was measured with TTC stain. In the in situ model, 39.9% +/- 4.2% of the ischemic zone was infarcted in control hearts but only 8.8% +/- 2.2% in preconditioning hearts. Pretreatment with MEC (5 mg/Kg) caused no alteration of infarct size in either non preconditioned (34.3% +/- 8.3%) or preconditioned hearts (6.7% +/- 3.3%). In isolated hearts, 45 minute ischemia caused 31.0% +/- 5.9% of the ischemic zone to be infarcted in control hearts and only 5.4% +/- 2.2% in preconditioned hearts. Pretreatment with ASP (1 mg/Kg) failed to affect infarct size in either non preconditioned (35.7% +/- 3.7%) or preconditioned hearts (10.2% +/- 1.9%). The data indicate that cyclooxygenase pathways are not involved in the preconditioning's protection.
 ...
PMID:Cyclooxygenase products are not involved in the protection against myocardial infarction afforded by preconditioning in rabbit. Cyclooxygenase pathway's involvement in preconditioning. 152 99

Considerable evidence has accumulated that oxygen free radicals play a major role in ischemic injury, particularly when followed by reperfusion. Few reports have demonstrated the occurrence of oxidative damage during the ischemic period, itself. Our laboratory has demonstrated that events occurring during an ischemic period with adequate oxygen supply can mimic the "oxygen paradox," using lipid peroxidation as an index of oxidative stress and lung edema as an index of tissue injury. The present study compares lipid peroxidation and oxidation of soluble (100,000g supernatant) protein during ischemia and reperfusion in isolated rat lung model perfused with artificial medium and ventilated with varying alveolar oxygen tension. Protein oxidation was determined by a modified dinitrophenylhydrazine (DNPH) method using Sephadex G-25 column chromatography to isolate the DNPH bound proteins. Global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. After 1 h ischemia in the isolated rat lung ventilated with 20% oxygen, protein carbonyls and thiobarbituric acid reactive substances (TBARS) increased significantly compared with controls. These changes were more pronounced after 60 min of reperfusion with 95% oxygen in the ventilation gas. With 0% oxygen (95% nitrogen and 5% CO2) content of the ventilating gas during ischemia, TBARS and protein carbonyls remained at the control level. The wet/dry weight ratio showed changes parallel to the indices of tissue oxidation. The presence of 5,8,11,14-eicosatetraynoic, an inhibitor of cyclooxygenase and lipoxygenase pathways, in the perfusate had no effect on the generation of protein carbonyls although inhibition of lipid peroxidation was demonstrated. This implies that the oxidation of soluble protein is not mediated by the eicosanoid metabolic cascade. These data indicate that oxidative processes occur during ischemia and are dependent on the alveolar oxygen concentration. Oxidation of soluble protein can be used as an index of oxidative damage during lung ischemia and reperfusion.
 ...
PMID:Role of oxygen in oxidation of lipid and protein during ischemia/reperfusion in isolated perfused rat lung. 160 29

The last two decades of research have produced detailed information not only on how ischemia causes degradation of phospholipids and accumulation of potentially cytotoxic breakdown products of such lipids, but also on reactions elicited by the subsequent conversion of these products into a series of lipids, mediating an array of cellular and intercellular reactions. It now seems clear that PAF, as well as several of the cyclooxygenase and lipoxygenase products of arachidonic acid, can induce changes, particularly in the microvasculature, which jeopardize cell survival in reperfused tissue. It is equally clear that, at least following long periods of ischemia, free radicals generated in reactions that are interacting with those producing eicosanoids and PAF play a similar role. A somewhat more speculative mechanism links sustained activation and membrane translocation of PKC to delayed neuronal death following transient ischemia. All of these interactions underscore the importance of lipolytic events for cell damage in ischemia and other conditions with a compromised cellular energy metabolism.
 ...
PMID:Ischemic brain damage: focus on lipids and lipid mediators. 163 6

Ischemically sensitive abdominal visceral afferents are known to reflexly stimulate the cardiovascular system. These nerve endings respond to severe hypoxia as well as to exogenously administered bradykinin and prostaglandins such as PGI2, PGE, and PGF2 alpha. We have shown previously that these prostaglandins can sensitize some previously unresponsive afferents to respond to ischemia. To determine if endogenously produced prostaglandins contribute to the observed increase in activity during ischemia, we recorded activity of 6 A delta- and 23 C-fiber sympathetic afferents in anesthetized cats during 5 min of ischemia before and 15-30 min after intravenous administration of either indomethacin (5 mg/kg) or aspirin (50 mg/kg). Before cyclooxygenase inhibition, we noted repeatable increases of 1.44 +/- 0.22 and 1.44 +/- 0.36 impulses/s in the A delta- and C-fibers, respectively, in response to ischemia. After indomethacin or aspirin, these increases were significantly reduced (P less than 0.05) in both thinly myelinated and unmyelinated afferents (0.69 +/- 0.36 and 0.46 +/- 0.21 impulses/s, respectively). In a second protocol, we observed that the activity of six A delta- and seven C-fibers was significantly reduced by aspirin or indomethacin when a single period of ischemia preceded cyclooxygenase blockade. These data, in conjunction with our previous observations, indicate that prostaglandins significantly contribute to the increased afferent discharge activity associated with ischemia of the abdominal visceral region.
 ...
PMID:Ischemically sensitive abdominal visceral afferents: response to cyclooxygenase blockade. 175 May 53


1 2 3 4 5 6 7 8 9 10 Next >>