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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.
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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.
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PMID:Cardiac and renal prostaglandin I2. Biosynthesis and biological effects in isolated perfused rabbit tissues. 34 5

To evaluate the effect of prostaglandin inhibition on the renal blood flow of the ischemic kidney, we administered indomethacin to 10 anesthetized dogs with renal artery stenosis and contralateral nephrectomy. Following the operation to produce renal ischemia, there was an increase of blood pressure associated with an increase of renin and the prostaglandins F1 (PGF1), and E (PGE). The administration of indomethacin to the intact, normotensive animals caused the anticipated decrease of prostaglandin E, renin, and renal blood flow. However, in the hypertensive dogs, indomethacin caused a paradoxical 45 per cent increase in the renal blood flow, despite a 44 per cent decrease of prostaglandin E. PGF1, PGE, renin, and erythropoietin exhibited the anticipated decreased levels. The study suggests that prostaglandins may not be the sole important factor in the regulation of renal blood flow in the presence of ischemia. Other important factors likely include the renin-sensitive angiotensin, the adrenergic, and the kallikrein-kinin systems.
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PMID:Paradoxical increase of renal blood flow in anesthetized hypertensive dog treated with indomethacin. 48

Radioimmunoassay was used to study the effects of renal ischemia on the distribution of PGE-like material between renal venous plasma and urine in anesthetized dogs. Renal venous and urinary concentrations of these substances were equal during control, ischemia and recovery periods. This relationship obtained despite significant increases in the concentration of PGE of both compartments during the ischemic insult. The renal secretion rates of PGE, calculated as the product of renal plasma flow and renal venous concentrations, was reduced during ischemia while urinary excretion, was unchanged. The evidence suggests that the increased PGE concentrations observed in both compartments during renal ischemia are primarily due to a dilutional factor rather than an increased synthesis. Furthermore, the data suggest that the net secretion of renal PG's per unit time may, in fact, be reduced during renal ischemia.
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PMID:Partition of PGE between renal venous plasma and urine during renal ischemia. 116 85

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.
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PMID:Ischemically sensitive abdominal visceral afferents: response to cyclooxygenase blockade. 175 May 53

Prostacyclin production in cultured cardiomyocytes is not induced by cellular ATP depletion per se, suggesting that the mechanism of ischemic injury is more complex. In the present study we subjected cultured ventricular myocytes to 'simulated ischemia' followed by reoxygenation. A slight increase in 6-keto-PGF(1 alpha) (the stable metabolite of PGI(2)) was found during 'ischemia', which continued to increase markedly during reoxygenation. PGE(2) levels were pronouncedly enhanced during ischemia but decreased during reoxygenation, and TXB(2) levels remained undetectable throughout. These findings reflect a cardiomyocyte response to anoxic injury, suggesting that they act to protect against cardiac injury by producing the potent vasodilators PGI(2) and PGE(2) during ischemia and reoxygenation.
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PMID:Oxygen deprivation and reoxygenation augment prostacyclin synthesis in cultured ventricular myocytes. 886 Jan 10

The accurate measurement of the chemical activators of pain in skeletal muscle has proved to be a major challenge. This study examined the applicability of microdialysis to the measurement of pain-producing substances in skeletal muscle using a defined model of ischemia and reperfusion in the rat. Microdialysis probes were placed into muscle of anesthetized rats. Ischemia was induced for 4 h, followed by reperfusion for 1 h. Perfusates were analyzed for hypoxanthine, potassium, prostaglandin (PG) E(2) and histamine. A 20-fold increase in perfusate hypoxanthine concentration was seen prior to reperfusion (70.1 +/- 27.1 microM for ischemic versus 3.7 +/- 1.9 microM for control; P < 0.05). An initial increase in PGE(2) concentration was seen during ischemia (7.4 +/- 2.0 nM versus 3.4 +/- 1.4 nM; P < 0.05) and immediately post-reperfusion (17.9 +/- 5.2 nM versus 4.0 +/- 1.1 nM; P < 0.05). Potassium concentration was significantly increased following occlusion and reperfusion. This indicates the applicability of microdialysis to the measurement of pain-producing substances in muscle during ischemia and reperfusion. Further use will provide novel information on muscle pain both in defined model systems and in clinical situations in humans.
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PMID:In vivo microdialysis-A technique for analysis of chemical activators of muscle pain. 1041 85

We aimed to investigate the cardio-protective role of taurine with low calcium level against reperfusion damage by adding taurine to extracellular fluid. Guinea-pig hearts were mounted on Langendorf perfusion apparatus and different compositions of perfusion solutions were prepared for each experimental group. After 20 min of normothermic ischemia the hearts were reperfused. Pre-ischemic, post-ischemic and post-reperfusion percentage changes of heart rate and contractile force were compared. Post-reperfusion tissue weight, malondialdehyde (MDA) and prostaglandin E-like activity (PGE-like activity) were assessed. Taurine-added low-calcium perfusion solution significantly decreased the postischemic myocardial injury.
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PMID:Taurine and calcium interaction in protection of myocardium exposed to ischemic reperfusion injury. 1046 51

Current methods of preserving lung tissue for transplantation are inadequate. In this study, we tested whether the combination of hypothermia plus prostaglandin E(1) (PGE(1)) treatment would have synergistic attenuation on ischemia-reperfusion (I/R) lung injury. Isolated rat lung experiments with ischemia for 1 h then reperfusion for 1 h, were conducted using six different perfusates: (1) University of Wisconsin solution (UW) at 30 degrees C (n = 5), (2) UW at 22 degrees C (n = 5), (3) UW at 10 degrees C (n = 4), (4) UW+PGE(1) at 30 degrees C (n = 4), (5) UW+PGE(1) at 22 degrees C (n = 4), and (6) UW+PGE(1) at 10 degrees C (n = 4). Hemodynamic changes, lung weight gain, capillary filtration coefficients, and lung pathology were analyzed to evaluate the I/R injury. Compared with 30 degrees C UW, animals treated with 22 degrees C UW and 10 degrees C UW had less I/R lung injury, with the groups receiving 22 degrees C UW showing superior results to group receiving 10 degrees C UW. The addition of PGE(1) to UW solution produced more attenuation of I/R injury than did UW alone. Among the six groups, 10 degrees C UW+PGE(1) produced the most reduction of I/R injury. This study has shown that hypothermia can attenuate I/R injury with the optimal flushing temperature being near 22 degrees C. PGE(1) also has a protective effect on I/R. Furthermore, hypothermia and PGE(1) have synergistic attenuation of I/R lung injury. We propose that pulmonary artery flushed with cooling UW+PGE(1) might improve lung preservation and improve results in lung transplantation.
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PMID:Hypothermia and prostaglandin E(1) produce synergistic attenuation of ischemia-reperfusion lung injury. 1050 24

Prostaglandin E(1) (PGE(1)) has cardioprotective effects on the ischemic-reperfused heart. To clarify the mechanisms underlying the protective action of PGE(1) on myocardium, we examined the effect of PGE(1) on the L-type Ca(2+) current (I(Ca)) using single atrial cells from rabbits. PGE(1) did not show a significant effect on basal I(Ca) but inhibited the I(Ca) prestimulated by isoproterenol (Iso, 30 nM). This inhibition was concentration dependent (EC(50) = 0.027 microM). Both sulprostone, a specific PGE receptor subtype (EP(1) and EP(3)) agonist, and 11-deoxy-PGE(1), an EP(3) agonist, inhibited the Iso-stimulated I(Ca), similar to PGE(1). Pretreatment with pertussis toxin (PTX) abolished the PGE(1) inhibition of I(Ca). Both the application of forskolin plus IBMX and intracellular dialysis with 8-bromoadenosine 3',5'-cyclic monophosphate eliminated the effect of PGE(1). PGE(1) did not show any further inhibition of I(Ca) when the effect of Iso was almost fully antagonized by acetylcholine. Methylene blue (guanylate cyclase inhibitor), KT-5823 (cGMP-dependent protein kinase inhibitor), and erythro-9-(2-hydroxy-3-nonyl)adenine (type II phosphodiesterase inhibitor) did not significantly change the inhibitory effect of PGE(1). These findings suggest that 1) PGE(1) inhibits Iso-stimulated I(Ca) by binding to the EP(3) receptor and 2) the PTX-sensitive and cAMP-dependent pathway is involved in the PGE(1) inhibition of I(Ca), but the nitric oxide-cGMP-dependent pathway is not. The PGE(1)-induced antiadrenergic effect shown in this study may contribute to the PGE(1) protection of myocardium against ischemia.
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PMID:EP receptor-mediated inhibition by prostaglandin E(1) of cardiac L-type Ca(2+) current of rabbits. 1051 71


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