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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of endothelin-1 (ET-1) and big ET-1 on coronary flow and contractile function was determined in isolated nonischemic and ischemic rat hearts. Both ET-1 (IC50 = 12 pMol) and big ET-1 (IC50 = 2 nMol) reduced coronary flow in a concentration-dependent manner, although ET-1 was > 100-fold more potent. Both compounds decreased contractility, an effect which was lost when coronary flow was held constant, indicating that ET-1 and big ET-1 decrease contractility secondary to reducing coronary flow. Mechanical reduction in coronary flow to levels equivalent to those seen for ET-1 or big ET-1 caused similar reductions in contractility. Both 30 pMol ET-1 and 10 nMol big ET-1 pretreatment significantly reduced the time to contracture in globally ischemic rat hearts, suggesting a proischemic effect. Phosphoramidon (100 microM, endothelin-converting enzyme inhibitor) and BQ-123 (0.3 microM, ETA receptor antagonist) abolished the preischemic increase in coronary perfusion pressure induced by big ET-1 as well as its proischemic effect, whereas only BQ-123 abolished the cardiac effect of ET-1. Neither phosphoramidon nor BQ-123 had an effect on severity of ischemia when given alone. Phosphoramidon was also given i.v. to rats subjected to coronary occlusion and reperfusion and was found to significantly reduce infarct size 24 hr postischemia. Thus, in isolated rat hearts, big ET-1 appears to be converted to ET-1 and is a potent coronary constrictor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of endothelin-1 and big endothelin-1 in modulating coronary vascular tone, contractile function and severity of ischemia in rat hearts. 146 21

Protective effects of cysteine (Cys), N-acetylcysteine (NAC), cysteamine (MEA), cystamine (CSSC) and aminopropylmethylisothiourea (APMT) on ischemia/reperfusion induced arrhythmias were studied in isolated Langendorff perfused rat hearts. The arrhythmias were caused by ligation of the anterior descending branch of the left coronary artery for 10 min and reperfused for 5 min. The drugs were dissolved in saline (NS) and perfused through a peristaltic pump system at 0.1, 0.6 or 3.6 mumol/min (n = 10), starting from 10 min before ligation up to 5 min after reperfusion. The control hearts were perfused with NS. The results showed that Cys, NAC and MEA pursued at 0.6-3.6 mumol/min significantly reduced the incidence of ventricular fibrillation (VF), which were 80-90% in control and 0-20% in 3 treated groups, with P less than 0.01-0.001. The duration of ventricular tachycardia (VT) + VF was 3.0 +/- 1.6 min in control and were 0.2 +/- 0.2, 0.2 +/- 0.1 and 1.2 +/- 2.1 min in Cys, NAC and MEA groups, respectively (with P less than 0.01-0.001). Coronary flow (CF) were remarkably reduced to about 50% during ligation in NS, but remained at normal levels in three treated groups. There were no significant protective effects on arrhythmias in CSSC and APMT perfused hearts. CF of CSSC and APMT groups were even less than those of control. The structure-activity analysis suggested that the SH group may play a crucial role in the protective effect of SH compounds on ischemia/reperfusion induced arrhythmias. The mechanism of protection was briefly discussed in this paper.
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PMID:[Protective effects of SH-compounds on ischemia reperfusion induced arrhythmias in the isolated rat heart]. 183 47

The reversibility of phosphoethanolamine transferase (EC 2.7.8.1) in rat brain is demonstrated in this paper. Microsomal ethanolamine glycerophospholipids were prelabeled with an intracerebral injection of [3H]ethanolamine 4 h before killing young rats. Labeled CDPethanolamine was produced by incubation of the microsomes with CMP, although to a lesser extent than for the previously observed release of CDPcholine. Ethanolamine and choline glycerophospholipids were labeled with [2-3H]glycerol by incubation with primary cultures of rat brain. Microsomes from rat brains, with diisopropyl phosphofluoridate for inhibition of lipases, were incubated with the labeled glycerophospholipids separately, and labeled diacylglycerols were produced. The kinetic parameters of phosphoethanolamine transferase and phosphocholine transferase (EC 2.7.8.2) were compared by incubating rat brain microsomes with [3H]CMP. Inclusion of AMP in the reaction mixture was necessary in order to inhibit the hydrolysis of CMP by an enzyme with the properties of 5'-nucleotidase (EC 3.1.3.5). For phosphoethanolamine transferase and phosphocholine transferase respectively, the Km values for CMP were 40 and 125 microM and the V values were 2.3 and 21.6 nmol/h per mg protein. The reversibility of both enzymes permits the interconversion of the diacylglycerol moieties of choline and ethanolamine glycerophospholipids. During brain ischemia, a principal pathway for degradation of ethanolamine glycerophospholipids may be by reversal of phosphoethanolamine transferase followed by hydrolysis of diacylglycerols by the lipase.
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PMID:A comparison of the reversibility of phosphoethanolamine transferase and phosphocholine transferase in rat brain microsomes. 301 Nov 1

N-Acylethanolamine phospholipids accumulate in rat brain during post-decapitative ischemia. Small amounts of these phospholipids consisting primarily of diacyl and alkenylacyl species can be detected within 15 min of ischemia and they increase linearly for 60 min. This ischemia-induced synthesis is more pronounced in developing rat brain (approx. 5.0 nmol/h per mumol lipid P) than in adult brain (0.4 nmol). Pulse labeling experiments with subcellular preparations of 10-day-old rat brain indicate a precursor-product relationship between ethanolamine phospholipids and their N-acyl analogs. N-Acylation of endogenous substrates occurs with both microsomes and mitochondria, exhibits a pH optimum of 10 and requires 1 mM Ca2+ for maximal (0.2 mM Ca2+ for half maximal) activity. Cell-free preparations of both developing and adult rat brain contain a phosphodiesterase which hydrolyzes N-acylphosphatidylethanolamine to phosphatidic acid and N-acylethanolamine. The latter is further hydrolyzed to fatty acid and ethanolamine by an amidohydrolase. [1-3H]Ethanolamine, injected intracerebrally or intraperitoneally into 13- and 18-day-old rats, is incorporated into brain ethanolamine phospholipids. Since small amounts of radioactivity are also associated with N-acylethanolamine phospholipids 5 and 24 h after injection of the substrate, it appears that these phospholipids may occur at a very low level as a natural lipid constituent of rat brain.
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PMID:N-acylethanolamine phospholipid metabolism in normal and ischemic rat brain. 373 Apr 13

The ability of the mixed endothelin (ETA/ETB) receptor antagonist (+/-)-SB 209670 to prevent and reverse ischemia-induced acute renal failure (ARF) was studied in rats with moderate and severe ARF. Uninephrectomized, chronically instrumented Sprague-Dawley rats were used. Moderate and severe ARF was induced by occlusion of the renal artery for 30 and 45 min, respectively. During the 24 hr after 30-min ischemia (moderate ARF), glomerular filtration rate (GFR) decreased by 95%, and fractional excretion of sodium increased from 0.6% to 10%. Infusion of (+/-)-SB 209670 at 10, 30 and 100 micrograms/kg.min for 30 min before, during and 60 min after renal ischemia had a moderate effect on renal function. Thus, with the highest dose, the ischemia-induced reduction in GFR was 70%. This dose, however, had no effect in rats when given before, during and after 45 min of renal ischemia (severe ARF). In contrast, when infused at 30 micrograms/kg.min for 3 hr on the day after ischemia, (+/-)-SB 209670 markedly increased survival rate (75%) in rats with severe ARF by significantly increasing tubular reabsorption of Na+, followed by a slow and gradual increase in GFR and reversal of the increase in plasma K+ concentration. Data from acute renal clearance studies in rats with moderate ARF showed that when infused 24 hr after ischemia, (+/-)-SB 209670 acutely reversed the impairment in sodium reabsorption without increasing GFR or renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonpeptide endothelin receptor antagonists. V: Prevention and reversal of acute renal failure in the rat by SB 209670. 756 50

The effects of intravenous (i.v.) infusions of exogenous endothelin-1 (ET-1, 0.05 and 0.1 nmol/kg/min) on incidence and severity of ventricular arrhythmias during 30-min period of acute myocardial ischemia were assessed in anesthetized rats. We examined the role of ETA-receptors in the proarrhythmic effects of both exogenous and endogenous ET using the ETA-receptor antagonist, BQ123. Exogenous ET-1 increased the severity and incidence of ischemic arrhythmias dose dependently. Both doses increased the total incidence of ventricular fibrillation (VF: from 30% in controls to 100 and 88% in rats given 0.05 and 0.1 nmol/kg/min ET-1, respectively); the higher dose also increased total arrhythmia count and duration of ventricular tachycardia (VT). BQ123 (10 micrograms/kg/min) completely abolished this proarrhythmic effect of exogenous ET-1. To assess the role of endogenous ET-1 in the genesis of ischemic arrhythmias, we studied the effects of a range of doses of BQ123 (5-100 micrograms/kg/min) on ischemic arrhythmias. Only one dose of BQ123 (10 micrograms/kg/min) attenuated arrhythmias by reducing total ventricular ectopic count (from 1,423 +/- 112 in controls to 677 +/- 159). The highest dose of BQ123 tested (100 micrograms/kg/min) increased arrhythmias by significantly increasing the incidence of irreversible VF (from 25 to 75%). These results suggest that exogenous ET-1 can aggravate ischemia-induced arrhythmias, an effect that is sensitive to ETA-receptor blockade. However, although endogenous ET-1 may make some contribution to the genesis of arrhythmias resulting from coronary occlusion through an action at ETA receptors, the observed proarrhythmic effect of BQ123 at high doses suggests that this may unmask an effect of ET-1 at other receptors.
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PMID:Effects of endothelin-1 and the ETA-receptor antagonist, BQ123, on ischemic arrhythmias in anesthetized rats. 759 33

1. Previous studies suggested that endothelin-1 (ET-1) may play a role in myocardial ischaemia and reperfusion. This study was designed to test the effect of a new nonpeptide antagonist of endothelin ETA and ETB receptors, bosentan, on myocardial infarct size, ventricular arrhythmias, and coronary endothelial dysfunction after ischaemia and reperfusion. 2. Anaesthetized male Wistar rats were subjected to 20 min ischaemia (left coronary artery occlusion) followed by 1 h (for the evaluation of coronary endothelial dysfunction) or 2 h (for the evaluation of infarct size) reperfusion, or 5 min ischaemia followed by 15 min reperfusion (for the evaluation of reperfusion arrhythmias). Vascular studies were performed on 1.5-2 mm coronary segments (internal diameter 250-300 microns) removed distal to the site of occlusion and mounted in wire myographs for isometric tension recording. Area at risk and infarct size were determined by Indian ink injection and triphenyl tetrazolium staining, using computerized analysis of enlarged sections after colour video acquisition. 3. Bosentan, administered at a dose which virtually abolished the pressor response to big ET-1 (3 mg kg-1, i.v. before ischaemia) did not affect heart rate, arterial pressure or the rate pressure product before ischaemia, during ischaemia and during reperfusion. Bosentan did not affect the incidence of reperfusion-induced ventricular fibrillation (controls: 86%, n = 14; bosentan: 93%, n = 15), and did not modify infarct size (% of area at risk: controls: 63 +/- 4, n = 10; bosentan: 60 +/- 6, n = 8). Ischaemia followed by reperfusion markedly reduced the endothelium-dependent relaxations to acetylcholine(maximal response: sham: 59 +/- 4%, n = 9; ischaemia-reperfusion: 26+/- 6%, n = 8; P<0.01), characteristic of reperfusion-induced endothelial dysfunction, and this dysfunction was not prevented by bosentan (maximal response to acetylcholine: 25 +/-5%, n = 9; P<0.01 vs sham; P = NS vs ischaemia/reperfusion).4. These experiments suggest that endogenous endothelin does not contribute to myocyte or coronary endothelial injury in this rat model of ischaemia and reperfusion.
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PMID:Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. 785 79

A comprehensive series of time-related behavioral, physiological and cerebral metabolic studies was conducted using conscious Sprague-Dawley rats to discern the anti-endothelin (ET) properties of the specific ETA receptor antagonist, FR139317. Endothelin-1 (9 pmol given by injection into one lateral ventricle, i.c.v.) produced convulsions, acute arterial hypertension, arterial hyperglycemia, and hyperventilation. Brain structures close to the i.c.v. site of injection, such as the caudate nucleus, lateral septal nucleus, corpus callosum and hippocampal CA3 medial lamellae, as well as 14 other individual structures, displayed moderate-to-intense levels of metabolic activation after endothelin. Data were assessed quantitatively by means of the autoradiographic [14C]deoxyglucose technique combined with image analysis. Neural circuits in the efferent projection paths of the stimulated forebrain structures, such as the midbrain oculomotor complex, amygdaloid nuclei, substantia nigra pars reticulata and caudal subicular subregions of the hippocampal formation, were stimulated focally by endothelin. Specific medullary nuclei and cerebellar cortical subregions displayed high rates of glucose metabolism following endothelin injection at the time of maximum behavioral and physiological stimulation. I.c.v. treatment with > or = 14 nmol FR139317 before endothelin significantly inhibited the effects produced by the peptide. At the highest dose of FR139317 (28 nmol), there was only mild behavioral stimulation following endothelin injection, and hypermetabolic responses in the brain were abolished except in two specific areas of the cerebellar cortex (approx 40% increases in metabolic activity in the copula pyramis and paramedian lobule). The results indicate that the cerebral stimulatory effects of i.c.v. endothelin are mediated by the A type of endothelin receptor. By itself, i.c.v. FR139317 had no effects on the parameters assessed. Further evaluation of FR139317 is warranted as a possible therapeutic agent for neuropathologies suspected of deriving from central neural or vascular stimulation by endothelin, such as aneurysmal vasospasm, ischemia, excitotoxicity, and peptide-mediated epilepsies.
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PMID:FR139317, a specific ETA-receptor antagonist, inhibits cerebral activation by intraventricular endothelin-1 in conscious rats. 786 51

We assessed the role of endogenous endothelin (ET) in reperfusion injury using a novel nonpeptidic ET antagonist of ETA and ETB receptors: bosentan (Ro 47-0203). In preliminary experiments in nonischemic rat hearts, we confirmed that bosentan 10(-5) M could block the changes in coronary flow (CF) and release of prostacyclin induced by ET-1 and the ETB-selective agonist sarafotoxin S6c (SRTX S6c). Thereafter, we induced global ischemia in paced hearts by closing the perfusion line for 20 min; this was followed by reperfusion. In one group of rats, bosentan (10(-5) M) was added to the perfusion medium before ischemia. In preischemic conditions, bosentan slightly increased CF by 14% (p = 0.094) in nonpaced hearts and by 35% (p = 0.001) in paced hearts, but did not influence cardiac contractility. Global ischemia produced severe ischemic damage, as shown by electromechanical dissociation (EMD) and decreased cardiac contractility. Bosentan did not influence recovery of cardiac function and did not ameliorate postischemic hemodynamic variables as compared with those of the control group. We conclude that endogenous ET does not play a major role in induction of reperfusion injury in isolated perfused rat heart.
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PMID:Role of endothelin during reperfusion after ischemia in isolated perfused rat heart. 789 67

Endothelin-1 (ET-1) is a potent cerebrovascular constrictor that has been implicated in brain ischemia. Utilizing the ETA receptor antagonist, BQ-123, the role of ET-1 in ischemic neuronal death following global ischemia was studied. BQ-123, administered ICV, either before and after ischemia or only after ischemia, increased hippocampal CA1 neuron survival in gerbils subjected to transient global ischemia. This study suggests that ETA receptor antagonists might be useful in neuronal salvage following stroke.
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PMID:Peptidic endothelin-1 receptor antagonist, BQ-123, and neuroprotection. 793 21


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