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

The present study addressed the acute effects of endothelin-1 on renal function and neutrophils accumulation in the setting of in vivo severe (60 min) acute ischemia/reperfusion. Ischemia/reperfusion decreased renal functional parameters and increased renal neutrophil accumulation and medullary congestion. All these parameters markedly improved with the intrarenal administration of anti-endothelin-1 antiserum. Comparatively, the intrarenal infusion of endothelin-1 decreased renal function and increased neutrophil accumulation. Abnormalities in renal histology were, however, less pronounced than with ischemia/ reperfusion. In experiments using rabbit isolated perfused kidneys, endothelin-1 induced the accumulation of labeled neutrophils. This accumulation was similar to that observed in kidneys obtained after 60 minutes of ischemia plus 60 minutes of reperfusion. Both endothelin and ischemia/ reperfusion effects were counteracted by an anti-endothelin antibody. In further in vitro studies, we found that endothelin-1-induced the expression of the CD18 antigens on the neutrophil surface. In subsequent experiments based on this effect of ET-1 on CD18 antigens, a blockade of both ischemia/reperfusion-induced and endothelin-1-induced neutrophil accumulation was obtained by infusion an anti-CD18 antibody. In conclusion, our experiments disclosed the critical role of endothelin-1 as a major promoter of early neutrophil accumulation after ischemia/reperfusion, which occurred through an integrin-mediated mechanism.
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PMID:Role of endothelin in the pathophysiology of renal ischemia-reperfusion in normal rabbits. 887 51

Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-alpha, IL-1-alpha and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-alpha, IL-1-alpha) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.
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PMID:Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain. 889 62

The role of endothelin ETA and ETB receptors as well as of nitric oxide (NO) and prostanoids in the effects of endothelin-1 on the coronary circulation was studied in anesthetized goats. Where blood flow in the left circumflex coronary artery (coronary blood flow) (electromagnetically measured), systemic arterial pressure, left ventricle pressure and d P/dt, and heart rate were recorded. Endothelin-1 (0.01-0.3 nmol), intracoronarily injected, produced marked, dose-dependent reductions in basal coronary blood flow, ranging from 5% for 0.01 nmol to 75% for 0.3 nmol; 0.1 and 0.3 nmol endothelin-1 also reduced systolic ventricle pressure and dP/dt. The effects of endothelin-1 on coronary blood flow were diminished during intracoronary infusion of BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp). specific antagonist for endothelin ETA receptors. 2-16 nmol/min) in a dose-dependent way, but not during the infusion of BQ-788 (N-[N-[N-[(2.6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-1-leucyl]-1- (methoxycarbonyl)-D-tryptophyl]-D-norleucine monosodium, specific antagonist for endothelin ETB receptors. 2-4 nmol/min). IRL 1620 (Suc-[Glu9, Ala11.15]endothelin-1-(8-21), specific agonist for endothelin ETB receptors. 0.01-0.3 nmol), intracoronarily injected. slightly reduced basal coronary blood flow only when 0.1 and 0.3 nmol were applied (maximal reduction about 25%); 0.3 nmol IRL 1620 also reduced systolic ventricle pressure and dP/dt. The effects of IRL 1620 were not modified by BQ-123 or BQ-788. NG-nitro-1-arginine methyl ester (L-NAME, inhibitor of NO synthesis, 47 mg/kg by i.v. route) reduced resting coronary blood flow by 10% and increased mean systemic arterial pressure and systolic ventricle pressure by 22 and 20%. respectively, without changing systolic ventricle dP/dt and heart rate. With L-NAME, the reductions of coronary blood flow by endothelin-1 were potentiated (P < 0.05), and those by IRL 1620 were not changed (P > 0.05). Meclofenamate (cyclooxygenase inhibitor, 4-6 mg/kg by i.v. route) modified neither the basal values of hemodynamic variables nor the coronary effects of endothelin-1 and IRL 1620. Therefore, endothelin-1 produces marked coronary vasoconstriction, which may be mediated by endothelin ETA receptors, with no participation of endothelin ETB receptors. NO, but not prostanoids, may produce a basal coronary vasodilator tone and may inhibit endothelin-1-induced coronary vasoconstriction. Also, it is suggested that the coronary vasoconstriction by endothelin-1 may impair cardiac performance due to heart ischemia.
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PMID:Coronary vasoconstriction by endothelin-1 in anesthetized goats: role of endothelin receptors, nitric oxide and prostanoids. 896 Aug 82

We have proposed that ischemic preconditioning in rabbit hearts is initiated by adenosine receptor stimulation resulting in activation of protein kinase C. If this theory is correct then any agonist which can activate PKC should also put the heart into a preconditioned state. This study sought to determine whether endothelin-1 (ET-1), which is known to activate protein kinase C can also mimic ischemic preconditioning. Isolated rabbit hearts experienced 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size was measured with triphenyltetrazolium chloride. In control hearts infarction was 30.3 +/- 2.5% of the risk zone. Preconditioning with 5 min global ischemia and 10 min reperfusion reduced infarct size to 5.6 +/- 0.7% (P < 0.01). Perfusion with either 10 PM ET-1 at constant coronary artery flow for 5 min in lieu of ischemia or 50 PM ET-1 with 10 nM nicardipine to block the former's coronary constructive effect was quite protective and equipotent with preconditioning. Infarction averaged 7.2 +/- 0.8% and 5.8 +/- 1.7% of the risk zone, respectively. This protection could be blocked by PD 156 707 (10 microM), a highly specific endothelin receptor antagonist. Chelerythrine (5 microM), a PKC inhibitor, also aborted protection (22.0 +/- 1.7% infarction). However, 8-(p-sulfophenyl)theophylline (100 microM), an adenosine receptor blocker, given during ET-1 administration did not block ET-1's protective effect indicating that adenosine was not involved in the effect. PD 156707 failed to block the protection from ischemic preconditioning (12.6 +/- 2.3% infarction) revealing that endothelin is not an important physiological mediator of ischemic preconditioning. We conclude that ET-1 can mimic ischemic preconditioning in isolated rabbit hearts as would be predicted since its receptors are PKC-coupled, but that endogenous endothelin contributes little to ischemic preconditioning.
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PMID:Pretreatment with endothelin-1 mimics ischemic preconditioning against infarction in isolated rabbit heart. 901 41

Longitudinal studies of large cohorts of patients with Raynaud's Phenomenon have addressed the predictors of developing a secondary disease. New insights have been reported into the pathogenesis of Raynaud's phenomenon and the consequences of ischemia. Studies have suggested that more than one defect may cause Raynaud's phenomenon, including increased alpha-2 sympathetic receptor activity on vessels, endothelial dysfunction, deficiency of calcitonin gene related peptide protein--containing nerves or some central thermoregulatory defect. The vasoconstricting and profibrotic cytokine endothelin-1 was found to be elevated in scleroderma but did not correlate with disease subset or with evidence of pulmonary hypertension. Oxidant stress is thought to be increased in scleroderma, causing tissue damage and provoking fibrosis. Treatment with infusion of prostacyclin for primary pulmonary hypertension was approved, paving the way for studies of secondary forms of pulmonary hypertension. Oral prostanoids are being tested for the treatment of Raynaud's phenomenon.
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PMID:Raynaud's phenomenon and other features of scleroderma, including pulmonary hypertension. 901 60

Ischemia reperfusion (I/R) injury is one of the leading cause of the transplanted organ loss. In this experimental study, we investigated the effect of captopril on endothelin and eicosanoid release in I/R injury of the kidney. Rats were subjected to 60 min ischemia and 60 min of reperfusion of the left kidney in control and captopril groups. Tissue protein oxidation products, PGE2 and LTB4 levels and plasma endothelin-1 (ET-1) like activity were determined in sham operated, control and captopril groups. There were no differences in the LTB4 levels among the groups. ET-1 and PGE2 levels and protein oxidation products increased in the control group when compared with the sham. Captopril further increased both PGE2 and ET-1 concentrations and prevented protein oxidation. The increased ET-1 concentrations in the captopril treated group may imply the protective role of endothelin as the significant increase in protein oxidation products was reversed by captopril infusion. This has led us to believe that captopril might be useful in preventing I/R injury of the kidney. Also the release of endothelin from the vascular endothelium is increased by captopril and may be mediated by PGE2.
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PMID:Captopril prevents the oxidative damage to proteins after renal ischemia reperfusion injury: role of endothelin-1. 904 33

Several peptide growth factors, including EGF, are known to protect endothelium from oxygen-related damage or ischemia-reperfusion, in vitro experiments show that such protective effect involves endogenous endothelium-related factors like nitric oxide and prostanoids. However, in vivo demonstrations of a possible role in related vascular diseases are lacking. In our experiments, human EGF and fraction C, a 3-10 kDa oligosaccharidic fraction from an aqueous extract of Triticum vulgare, known as growth promoters for several cell types including endothelial cells, were found protective against ischemic necrosis of the mouse tail induced by i.v. k-carrageenin plus endothelin-1. After i.p. injection, peak activities were observed at 10 micrograms/kg EGF and 2 mg/kg fraction C. Pretreatment with L-NAME reduced protection in a dose-dependent manner. Addition of indomethacin increased the effect of L-NAME, suggesting that both nitric oxide and eicosanoids are involved in the protective effect of EGF and fraction C.
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PMID:Protective action of epidermal growth factor and a fraction from Triticum vulgare extract in mouse tail necrosis. 907 27

This study was conducted to clarify the role of endothelin-1 in the portal vein after hepatic ischemia/ reperfusion and to ascertain whether it is related to hepatic microcirculation disturbance. Using a canine ischemic liver model, the portal and systemic endothelin-1 levels were measured before ischemia, then after 1 h and 2 h of reperfusion, and comparatively evaluated with the serum levels of GOT and lactic dehydrogenase (LDH). As an indicator of liver tissue microcirculation, tissue blood flow volume (TBF) was also measured in the site subjected to ischemia. The animals were divided into: group 1, which received ischemia for 30 min; group 2, which received ischemia for 60 min; and group 3, which received a sequence repeated four times of 15 min ischemia and 10 min reperfusion. The portal endothelin-1 level became significantly elevated after reperfusion compared to that before ischemia in all groups, being significantly higher in group 2 than in the other groups. The systemic endothelin-1 level also increased after reperfusion; significantly in group 2. The portal endothelin-1 level was generally higher than the systemic level, which again was statistically significant in group 2. After 2 h of reperfusion, a significant positive correlation was found between the portal endothelin-I level and serum LDH, whereas a significant negative correlation was found between the portal endothelin-1 level and TBF. The finding that the portal endothelin-1 level became elevated after hepatic ischemia/reperfusion suggests that it probably plays an essential role in hepatic ischemia/ reperfusion injury by adversely influencing tissue microcirculation.
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PMID:Endothelin-1 levels in portal venous blood in relation to hepatic tissue microcirculation disturbance and hepatic cell injury after ischemia/reperfusion. 908 47

At peak exercise, plasma endothelin-1 concentration increases in patients with effort angina as well as thallium-201 radionuclide perfusion defects; the opposite occurs in patients with normal scans and in healthy volunteers. It is concluded that exercise-induced ischemia correlates with enhanced endothelin-1 production.
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PMID:Relationship between plasma endothelin-1 levels and myocardial ischemia induced by exercise testing. 910 11

The purpose of this study was to determine the antagonistic effect of tetramethyl pyrazine (TMP), a sort of chinese herbal medicine, on coronary vasoconstriction induced by endothelin-1 (ET-1) in closed chest dogs. ET-1 at doses of 50, 75 and 100 pmol was selectively administered into left main coronary artery and coronary angiogram was performed in 1, 3 and 10 minutes after intracoronary administration of ET-1. After a 60 minute interval ET-1 administration and coronary angiogram were repeated in two groups in group A with 5 dogs intravenous infusion of saline solution was administered while in group B with 4 dogs TMP was infused at a dose of 80 mg/kg. Blood pressure of intra-femoral artery, heart rate and ECG were monitored during the experiment. The study demonstrated that coronary vessel diameter significantly decreased by 17% (P < 0.02) in group A and 20% (P < 0.02) in group B, associated with ischemia in ECG (4/5 in group A and 3/4 in group B) after intracoronary administration of ET-1. Endothelin-1 induced coronary vasoconstriction and ischemic changes in ECG were significantly inhibited by intravenous TMP. The coronary diameter increased by 20% (P < 0.03) after administration of TMP, comparing with the control group. Heart rate had an increased response to TMP. In conclusion this study demonstrated that intracoronary administration of ET-1 caused significant myocardial ischemia through coronary vasoconstriction, which was inhibited by TMP. TMP significantly dilated coronary artery.
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PMID:[Effect of tetramethyl pyrazine on coronary vasoconstriction induced by endothelin-1 in dogs]. 920 4


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