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

Serum levels of the vasoconstrictor endothelin-1 (ET-1) increase in ischemia and systemic hypertension. We examined the effects of ET-1 on the cochlear microvasculature. Blood vessels were cast with methacrylate in adult male Wistar Kyoto rats, 10 min after intravenous injection of ET-1 (1.0 microg/kg); control animals received saline. Systemic blood pressure was recorded continuously. ET-1 increased the average systolic pressure by 18% and average diastolic pressure by 22% (P < 0.01). Scanning electron microscopy of cast vessels showed multiple circumscribed luminal constrictions on: (1) postcapillary venules; (2) collecting veins; (3) where collecting veins merged with the spiral modiolar vein; (4) on the spiral modiolar vein itself. Circumscribed constrictions in arteries were not observed. In ET-1 injected animals focal contractions of collecting veins reduced luminal width by 13.4% +/- 2.9 (P < 0.01). In control rats, constrictions on venous casts were minimal and constrictions on arteries were not observed. The present study shows that ET-1 is involved in local control of cochlear blood flow in that it focally contracts cochlear veins. It is suggested that this might be due to the high affinity of ET-1 receptors and/or the large number of ET-1 receptors on contractile cells in venous walls.
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PMID:Endothelin-1 causes luminal constrictions in rat cochlear veins. 936 27

In this study, the involvement of osteopontin in a rat model of ischemia-induced acute renal failure (ARF) was evaluated. In unilaterally nephrectomized Sprague Dawley rats where the left artery was occluded for 30 min., plasma creatinine levels increased significantly within two hours following reperfusion indicating the onset of renal failure. Northern analysis of kidney cortical RNA from these rats showed a time-dependent increase in osteopontin mRNA expression that was significantly higher than sham-operated rats. Since endothelin-1 (ET-1) is implicated as a mediator of acute renal failure, we evaluated its effects on osteopontin expression in a rat mesangial cell-line. Data from in vitro studies indicated that endothelin-1 (ET-1) caused a modest but reproducible increase in osteopontin mRNA in these cells. While the signal for osteopontin upregulation in the rat model is not known, ET-1, which is known to be increased during ischemia, may contribute at least in part to this process.
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PMID:Upregulation of osteopontin in ischemia-induced renal failure in rats: a role for ET-1? 940 59

Renal endothelin-1 (ET-1 ) production is increased by hypoxia and has been implicated in ischemia-induced renal hypoperfusion. Because the inner medullary collecting duct (IMCD) is a major source of ET- 1 in the kidney, and because ET- 1--in the setting of ischemic renal failure-may alter medullary perfusion, we sought to determine whether hypoxia modulated ET-1 production by IMCD cells. Primary cultures of rat IMCD cells were exposed to 21%, 3%, or 0%O2. IMCD ET-1 secretion significantly increased after exposure of cultures to 3% O2 (114.1% +/- 4.7% increase over control value) and 0%O2 (171.7% +/- 7.9% increase). ET-1 mRNA levels, as determined by reverse transcription-polymerase chain reaction, also increased 2.5-fold after 24-hour exposure to 0% O2. We speculate that a hypoxia-induced increase in IMCD ET-1 production plays a role in modulating renal medullary perfusion during ischemic renal failure.
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PMID:Hypoxia regulates endothelin-1 production by the inner medullary collecting duct. 945 26

The beta-amyloid (A beta 1-40) peptide has previously been shown to enhance phenylephrine contraction of aortic rings in vitro. We have employed a novel observation, that A beta peptides enhance endothelin-1 (ET-1) contraction, to examine the relationship between vasoactivity and potential amyloidogenicity of A beta peptides, the role played by free radicals and calcium in the vasoactive mechanism, and the requirement of an intact endothelial layer for enhancement of vasoactivity. Rings of rat aortae were constricted with ET-1 before and after addition of amyloid peptide and/or other compounds, and a comparison was made between post- and pre-treatment contractions. In this system, vessel constriction is consistently dramatically enhanced by A beta 1-40, is enhanced less so by A beta 1-42, and is not enhanced by A beta 25-35. The endothelium is not required for A beta vasoactivity, and calcium channel blockers have a greater effect than antioxidants in blocking enhancement of vasoconstriction by A beta peptides. In contrast to A beta-induced cytotoxicity, A beta-induced vasoactivity is immediate, occurs in response to low doses of freshly solubilized peptide, and appears to be inversely related to the amyloidogenic potential of the A beta peptides. We conclude that the mechanism of A beta vasoactivity is distinct from that of A beta cytotoxicity. Although free radicals appear to modulate the vasoactive effects, the lack of requirement for endothelium suggests that loss of the free radical balance (between NO and O2-) may be a secondary influence on A beta enhancement of vasoconstriction. These effects of A beta on isolated vessels, and reported effects of A beta in cells of the vasculature, suggest that A beta-induced disruption of vascular tone may be a factor in the pathogenesis of cerebral amyloid angiopathy and Alzheimer's disease. Although the mechanism of enhanced vasoconstriction is unknown, it is reasonable to propose that in vivo contact of A beta peptides with small cerebral vessels may increase their tendency to constrict and oppose their tendency to relax. The subclinical ischemia resulting from this would be expected to up-regulate beta APP production in and around the vasculature with further increase in A beta formation and deposition. The disruptive and degenerative effects of such a cycle would lead to the complete destruction of cerebral vessels and consequently neuronal degeneration in the affected areas.
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PMID:Characteristics of the in vitro vasoactivity of beta-amyloid peptides. 951 24

The ability of hexarelin, a recently synthesized hexapeptide with a remarkable growth hormone (GH)-releasing activity, to reverse signs of cardiovascular dysfunction in GH-deficient animals was studied in young male rats made GH deficient by the administration of an anti-GH-releasing hormone serum (GHRH-Ab) for 20 days. Heart preparations from GHRH-Ab treated rats, subjected to low-flow ischemia and reperfusion, showed: a progressive increase of left ventricular end-diastolic pressure during the ischemic period and a poor recovery of contractility at reperfusion as compared to control hearts; a decreased rate of formation of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, in perfusates of both preischemic and reperfusion period; an increased vasopressor activity of angiotensin II on the coronary vasculature. The endothelium-dependent relaxing function in GH-deficient rats was also evaluated in aortic ring preparations, which showed: a decreased rate of formation of 6-keto-PGF1 alpha, an hyperreactivity to endothelin-1, a markedly reduced vasopressor response to NG-monomethyl-L-arginine (the nitric oxide synthase inhibitor) and a decreased vasodilator response to acetylcholine of precontracted aortic tissue. Hexarelin (80 micrograms/kg, s.c. twice daily), administered for 15 days to GHRH-Ab-treated rats, fully restored the somatotropic function and reversed all the signs of cardiac and endothelial dysfunction. In fact, in heart preparations from rats treated with hexarelin the trend of the ischemic damage was similar to that observed in control rats and both the rate of formation of 6-keto-PGF1 alpha and the vasopressor activity of angiotensin II were reverted to control levels. Furthermore, all the parameters of endothelial function were in the normal range. These results indicate that GH deficiency in rats is responsible for an impairment of cardiac function that is associated with a damage of the endothelium-dependent relaxing function not limited to coronary vessels but widespread in the circulation. These alterations are fully reverted by an in vivo treatment with hexarelin.
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PMID:Hexarelin, a growth hormone-releasing peptide, discloses protectant activity against cardiovascular damage in rats with isolated growth hormone deficiency. 953 9

The aim of the present study was to test the hypothesis that the vasoconstrictive peptide endothelin-1 is upregulated in ischemia and reperfusion in skeletal muscle. Sixty-eight Wistar rats were included in the series: 12 served as controls that did not undergo the procedure, 16 underwent sham operations, and 40 were subjected to a modified tourniquet ischemia for 3 hours and 20 minutes. Of the 40 rats, 16 were killed at the end of the ischemic period, 16 underwent reperfusion for 2 hours, and eight underwent reperfusion for 72 hours. Areas of necrosis were measured by morphometry in hematoxylin and eosin-stained cross sections of the anterior tibial muscles that had been reperfused for 72 hours. Sections from the controls, the muscles that had not been reperfused, and the reperfused muscles were immunostained for endothelin-1. Serum endothelin-1 levels in blood samples from the aorta were determined with a commercial enzyme immunoassay kit. The anterior tibial muscle was harvested for preproendothelin-1 mRNA analysis with RNase protection assay. The hematoxylin and eosin-stained sections showed extensive necrosis with an acellular core of no reperfusion. The muscular core demonstrated weak immunostaining for endothelin-1 in all sections, a subfascial narrow brim of fibers showed enhanced immunoreactivity at the end of ischemia, and all fibers outside the core stained by 2 hours after the start of reperfusion. After 72 hours of reperfusion, the fibers outside the core stained positive in a checkerboard-like pattern. There were no differences in serum endothelin-1 levels between the groups. Preproendothelin-1 mRNA analysis with RNase protection assay showed 2-fold upregulation at the end of ischemia and 4-fold upregulation after 2 hours of reperfusion (p = 0.001). This study supports the hypothesis that both ischemia and reperfusion upregulate endothelin-1 in skeletal muscle.
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PMID:Endothelin-1 is upregulated during skeletal muscle ischemia and reperfusion. 956 85

The purpose of this study was to determine whether treatment with an endothelin-1 (ET-1)-receptor antagonist could prevent ET-1-mediated ischemia-reperfusion injury and early allograft dysfunction. Eleven dogs were subjected to left lung allotransplantation. Donor lungs were preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 h. Animals received an intravenous infusion of either the ET-receptor antagonist SB209670 (n = 6) (15 microg/kg/min) or saline (control, n = 5), in a blinded fashion. The infusion started 30 min before transplantation and continued for up to 6 h after transplantation. Hemodynamic measurements, blood gas tensions, and plasma samples were obtained with animals functioning solely on the transplanted lung. Open-lung biopsies were obtained for wet-to-dry-weight ratios and histologic and immunohistochemical analyses. Survival at 6 h after transplantation was 40% in the control group and 100% in the treatment group. Pulmonary vascular resistance and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals at 3 and 6 h after transplantation. Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control group. Arterial and venous plasma ET-1 concentrations increased after transplantation; however, they were significantly higher in the treatment group. Immunohistochemical analysis revealed more intense ET-1 immunostaining in the airways and parenchyma of the treatment group. We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reperfusion injury, resulting in improved graft function and survival after lung transplantation.
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PMID:Efficacy of administering an endothelin-receptor antagonist (SB209670) in ameliorating ischemia-reperfusion injury in lung allografts. 962 Sep 35

The effects of ZK-118.182, a stable analogue of PGD2, were evaluated in an endothelin-1-induced cerebral ischemia rabbit model. Ischemia was induced by endothelin-1 injection (0.25 ng bolus) into subcavian artery and ischemic changes were assessed histologically by the number of ischemic neurons in the brain stem. ZK-118.182 (2 micrograms/kg, bolus into subclavian artery) reduced the number of ischemic neurons when injected 20 min after endothelin-1 injection, Iloprost, a stable analogue of PGI2, was also effective in reducing the number of ischemic neurons in a dose of 0.5 microgram/kg (bolus into subclavian artery). The results suggested that ZK-118.182 has a potent antiischemic effect which is comparable to that of iloprost in rabbits.
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PMID:Antiischemic effect of ZK-118.182 in rabbits: a comparative study with iloprost. 965 84

The vasodilator nitric oxide (NO) is involved in the regulation of systemic blood pressure and local organ blood flow. Inhibitors of the constitutively expressed nitric oxide synthase in endothelial cells (eNOS), e.g., Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME), aggravated liver injury in a variety of models. On the other hand, inhibitors of the inducible NOS (iNOS), e.g., 2-aminoethyl-isothiourea (AET), were found to be beneficial during endotoxemia. The aim of this investigation was to study the effect of AET compared with L-NAME on liver microvascular blood flow and injury in more complex models with multiple insults, i.e., ischemia (20 min)-reperfusion (8 h) in combination with .5 mg/kg endotoxin (IRE). Male Fisher rats were treated with 10 mg/kg AET or L-NAME and subjected to IRE. At 8 h, liver injury (plasma ALT: 1320+/-164 U/L) was significantly increased in AET-treated (5,018+/-1,379 U/L) and L-NAME-treated groups (2,429+/-228 U/L). Each inhibitor attenuated microvascular blood flow (assessed by laser Doppler flowmetry) to a similar degree. In striking contrast, AET completely reversed the endotoxin-induced impairment of the microvascular blood flow and significantly protected against an endotoxin-induced liver injury (plasma ALT: 3,007+/-268 U/L (ET); 460+/-39 U/L (ET+AET)). Infusion of endothelin-1 reduced microvascular blood flow by 50-60% and caused liver injury. Our data demonstrated that an inhibitor of eNOS (L-NAME) has a consistent detrimental effect on liver injury during ischemia-reperfusion and endotoxemia mainly because it can cause additional ischemia by reducing the microvascular blood flow. However, selective inhibitors of iNOS (AET) can impair hepatic blood flow and aggravate the injury or improve blood flow and attenuate organ injury depending on the experimental model. These results suggest that iNOS inhibitors may not be universally beneficial and should be tested in a variety of experimental models of sepsis/endotoxemia before used in clinical settings.
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PMID:Differential effect of 2-aminoethyl-isothiourea, an inhibitor of the inducible nitric oxide synthase, on microvascular blood flow and organ injury in models of hepatic ischemia-reperfusion and endotoxemia. 968 86

Evidence has been provided that increased portal vein pressure results in increased release of endothelin-1 (ET-1). Strangulation obstruction is associated with increased venous pressure, and we wanted to determine if it is associated with increased local release of ET-1 and elevated concentration of ET-1 in systemic blood. Strangulation obstruction was induced by elevating pressure in a gasket placed around a loop of ileum until venous pressure reached 50 mm Hg. Ischemia in a bowel loop was induced by arterial clamping, reducing blood flow by 70%. Blood samples were collected before and after 30, 90, and 180 min of strangulation or ischemia. ET-1 was determined by radioimmunoassay following acidification and extraction on C18 columns. In strangulated loop the blood flow decreased by 70%. ET-1 concentration remained around 5 pg/ml in arterial blood, increased fourfold in strangulated venous blood, and remained unchanged in venous blood from control bowel. The release of ET-1 from the strangulated loop to blood increased twofold. Ischemia resulted in reduced release of ET-1. It is concluded that strangulation obstruction causes increased release of ET-1 to venous blood in the strangulated loop, but not increased ET-1 concentration in systemic blood. The increased ET-1 release was probably due to increased venous pressure, not to low blood flow.
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PMID:Release of endothelin-1 in strangulation obstruction of the small bowel in pigs. 973 44


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