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)

The pathophysiologic effects of cocaine on neuronal, pulmonary, and cardiovascular tissue are related to the drug's interaction with select catecholamine and neuroendocrine systems. Cocaine has been shown to alter circulating levels of the neurotransmitters, dopamine, norepinephrine, epinephrine, as well as the hypothalamic-pituitary-adrenal axis hormones corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Furthermore, brain and lung tissue have been identified as primary sites of cocaine sequestration and metabolism. This paper reviews evidence suggesting that steroid-potentiated actions of catecholamines on vascular tissues contributes to the etiology of cocaine-related medical complications, including ischemic stroke, coronary ischemia, and ischemia-based renal failure.
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PMID:Brain, lung, and cardiovascular interactions with cocaine and cocaine-induced catecholamine effects. 133 74

This experiment tested the hypothesis that corticotropin-releasing factor (CRF) contributes to hippocampal ischemic injury. The antagonist to CRF (alpha-CRF) was administered intraventricularly 15 min prior to 10 min of transient forebrain ischemia in the Wistar rat. alpha-CRF demonstrated a neuroprotective effect in a dose-dependent manner most notable in CA1. There was also an increase in postischemic EEG recovery. It is postulated that CRF contributes to hippocampal ischemic injury through increased neuronal activity.
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PMID:Corticotropin releasing factor antagonist reduces ischemic hippocampal neuronal injury. 186 56

Three structurally related peptides, ovine corticotropin-releasing factor, sauvagine, and urotensin I are selective mesenteric vasodilators in dogs. To assess the possible benefit of these peptides in nonocclusive mesenteric ischemia, they were compared with a nonselective vasodilator, sodium nitroprusside, in the anesthetized dog. Mesenteric blood flow was reduced by approximately 30%, without lowering of systemic arterial pressure, by either digoxin or pericardial tamponade. In the digoxin model, i.v. infusions of corticotropin-releasing factor, sauvagine, and urotensin I restored intestinal vascular resistance and mesenteric blood flow to control values, without causing a fall in systemic arterial blood pressure. In the tamponade model, only urotensin I was assessed, and it produced the same restoration of hemodynamic variables. On the other hand, in both models, i.v. infusions of nitroprusside, which were effective in correcting intestinal vascular resistance, produced a fall in arterial blood pressure (presumably because of systemic dilatation), which prevented restoration of mesenteric blood flow. Intestinal oxygen uptake was not altered by tamponade, but was reduced by 23% in the digoxin model, where it was restored to control values by both the peptides and nitroprusside. The increased oxygen extraction seen in both models was corrected by the peptides but not by nitroprusside, suggesting that nitroprusside may have a direct and offsetting metabolic effect on the gut.
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PMID:Use of selective mesenteric vasodilator peptides in experimental nonocclusive mesenteric ischemia in the dog. 348 10

Three synthetic peptides, ovine corticotropin-releasing factor, sauvagine, and urotensin I, contain homologous amino acid residues. In the anesthetized dog, all three produce marked and selective dilatation of the mesenteric circulation; none of the peptides influenced blood flow in the renal, femoral, carotid, or even celiac arteries. The mesenteric vasodilatation appeared to be unrelated to the common ability of these peptides to release corticotropin and beta-endorphin, and cannot be abolished or attenuated by conventional blocking agents or inhibitors. The unique action of these peptides suggests that there may be a related peptide in the intestine that acts to regulate intestinal blood flow. The peptides may also prove useful therapeutically in nonocclusive ischemia, if this unusual action is also present in humans.
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PMID:Corticotropin releasing factor-like peptides produce selective dilatation of the dog mesenteric circulation. 632 56

Corticotropin-releasing hormone (CRH) antagonism has neuroprotective effects in models of ischemia. We examined CRH mRNA by in situ hybridization in a well-established rat model of focal cerebral ischemia caused by permanent middle cerebral artery occlusion (MCAo). In ischemic cortex CRH mRNA levels were elevated 2.6-fold 60 min after MCAo, compared with sham operated animals. CRH mRNA was also induced in the amygdala, 60 min following ischemia, in a pattern which was qualitatively different from that of sham operated animals. This rapid and profound increase in CRH mRNA levels during focal cerebral ischemia is likely to be associated with neurotoxicity, as CRH antagonism has been reported to cause a significant reduction in neuronal loss during ischemia.
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PMID:Focal cerebral ischemia induces CRH mRNA in rat cerebral cortex and amygdala. 854 82

Corticotropin-releasing factor (CRF), a peptide neurotransmitter, is suggested as a novel agent to reduce reperfusion edema following ischemia. In a rat hind limb replantation model, animals underwent amputation followed by 2.5 hours of ischemia with replantation and 2 hours of reperfusion. Animals were randomized to seven groups: a nonischemic control group and six experimental groups receiving treatment prior to reperfusion with (1) saline control, (2) alpha 9,41-CRF-a CRF receptor blocking agent (98 micrograms/per kilogram), (3) subcutaneous CRF (320 micrograms/per kilogram), (4) intravenous CRF (80 micrograms/per kilogram), (5) alpha-CRF and subcutaneous CRF, and (6) alpha-CRF and intravenous CRF. Comparison of preischemic amputated limb weight with weight after ischemia and reperfusion showed a reproducible and significant gain in limb weight after 2 hours (p = 0.004). A significant reduction in limb weight gain (49%) was achieved with both subcutaneous (p < 0.04) and intravenous CRF (p < 0.036). With the dose used in this model, alpha 9,41 CRF attenuated but did not completely block the effects of intravenous or subcutaneous CRF.
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PMID:Reduction of ischemic reperfusion edema with corticotropin-releasing factor (CRF) in rat hind limb replantation. 911 4

Rats treated with the neuroepileptic drug, kainic acid, exhibit a specific regional pattern of neurodegeneration 24 h following onset of acute limbic status epilepticus. At 24 h post-seizure, the areas undergoing neurodegeneration also exhibit substantial amounts of the neuropeptide corticotropin-releasing factor (CRF) which is not present under normal conditions. In experimental brains, CRF is localized immunocytochemically to cells and densely labeled fibers in areas with neurodegeneration. Networks of CRF fibers closely surround moribund neurons staining intensely for acid fuchsin. Acid fuchsin, an acidophilic dye, is used routinely as a marker for irreversible neuronal injury, and acid fuchsin-positive neurons are identified in specific areas affected by kainic neurotoxicity. Evidence exists in the literature that CRF functions in brain as a excitatory neurotransmitter/neuromodulator. Under certain pathological conditions (i.e., seizures, brain trauma, ischemia), it has been postulated that CRF could act as an neurotoxic agent. This study provides anatomical evidence that CRF may function following seizures as an neurotoxin because of the close proximity of CRF-labeled fibers to degenerating neurons.
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PMID:Corticotropin-releasing factor--immunolabeled fibers in brain regions with localized kainate neurotoxicity. 1060 38

Recently, the ectopic expression of corticotropin-releasing factor (CRF) has been suggested as being associated with processes linked to neuronal injury and/or degeneration in response to a brain insult. However, there is little experimental data linking CRF directly to neuronal death induced by ischemia. Therefore, in the present study, we investigated the temporal and spatial alteration of CRF and its binding protein expressions in the hippocampus after transient ischemia. As a result, we found the selective increase of CRF immunoreactivity in the CA1 pyramidal cells and their processes at only 4 days post-ischemic insult. In contrast, CRF binding protein immunoreactivity was rarely detected in the CA1 region. These results suggest that transient ischemia may provoke selectively ectopic expression of CRF, but not of its binding protein, in vulnerable regions, and this enhancement of CRF may play important roles in the neurodegenerative process.
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PMID:Expression of corticotropin releasing factor, but not its binding protein, in CA1 pyramidal cells of gerbil hippocampus following transient ischemia. 1131 88

The neuroprotective effects of a systemically active, highly selective, corticotropin-releasing factor-1 (CRF1) receptor antagonist, R121920 ((7-(dipropylamino)-2,5-dimethyl-3- [2-(dimethylamino)-5-pyridyl] pyrazolo [1,5-a] pyrimidine), was assessed in two rat models of permanent focal cerebral ischemia, where the middle cerebral artery (MCA) was occluded either through the subtemporal approach or using the intraluminal suture technique. R121920 rapidly crossed the blood-brain barrier after intravenous (IV) bolus administration (10 mg/kg), with peak brain concentrations at 5 minutes (2.26 +/- 0.40 microg/mL), which were approximately 2-fold greater than those in plasma (0.98 +/- 0.24 microg/mL). Treatment with R121920 (10 mg/kg IV followed by 5 mg/kg subcutaneously at hourly intervals for 4 hours) significantly (P < 0.001) reduced total (by 40%) and cortical (by 37%) infarct volume at 24 hours after subtemporal MCA occlusion (MCAO). In the intraluminal suture MCAO model, IV administration of R121920 (10 mg/kg) at the time of ischemia onset (and at multiple times thereafter) reduced both hemispheric infarct volume (by 34%, P < 0.001) and brain swelling (by 50%, P < 0.001) when assessed at 24 hours. In this model of focal ischemia, significant reduction (P < 0.05) in both outcome measures was obtained when R121920 administration was delayed up to 1 hour after MCAO. These results further define the antiischemic properties of selective CRF 1 antagonists in two experimental models of permanent focal cerebral ischemia.
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PMID:Neuroprotective effects of the CRF1 antagonist R121920 after permanent focal ischemia in the rat. 1159 98

Urocortin (Ucn) is a new member of the corticotropin-releasing factor (CRF) neuropeptide family and has positive inotropic actions and protective effects against ischemia in the rat heart. Ucn binds with very high affinity to both CRF receptor type 1 (CRF-R1) and CRF receptor type 2 (CRF-R2). However, to date, endogenous ligand(s) for CRF receptors expressed in the human heart have yet to be elucidated. In this study, we therefore examined the expression of Ucn and CRF receptors in human heart obtained at autopsy by RT-PCR, immunohistochemistry, and RIA. RT-PCR analysis demonstrated that Ucn and CRF-R2alpha mRNAs were detected in all four chambers. CRF-R1 mRNA was weakly present in some left atria, left ventricles, and in one right ventricle. CRF-R2beta mRNA was detected predominantly in the left atrium. CRF mRNA was not detected in any of the four chambers. Immunostaining for both Ucn and CRF receptors was detected in cardiac myocytes in all four chambers. Ucn-like immunoreactivity was detected in all four chambers by RIA, with the highest concentrations in the left ventricle (1.90 +/- 0.5 pmol/g wet weight, mean +/- SEM; n = 4). On the other hand, CRF-like immunoreactivity was very low or undetectable in the human heart. Sephadex G-50 column chromatography demonstrated that most of the Ucn-like immunoreactivity in the human heart was eluting earlier than the standard Ucn, with one minor peak in the position for Ucn. Ucn immunoreactivity was not detected in skeletal muscle by immunohistochemistry or RIA. These results suggest that Ucn is produced in the human heart and stored there mainly in the larger molecular weight forms. Endogenously produced Ucn may therefore exert its effects mostly through CRF-R2 in an autocrine and/or paracrine manner in the human heart.
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PMID:Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. 1205 Feb 87


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