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

The pathogenesis of primary Raynaud's phenomenon remains an enigma. Most evidence favors a local abnormality in the digital arteries as opposed to an increased activity of the sympathetic nervous system. The local fault may involve the alpha 2-adrenergic receptors, which are most important in reflex sympathetic vasoconstriction. Cooling blood vessels increase the sensitivity of alpha 2-adrenergic receptors, increased levels of alpha 2-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to alpha 2-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of beta-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit. New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial.
 ...
PMID:Raynaud's phenomenon. An update. 202 4

Changes in the levels of histamine, monoamines, and their metabolites in the cerebral cortex and striatum after occlusion of the middle cerebral artery in rats were examined. The water content of the ipsilateral brain regions gradually increased after occlusion. In the ischemic side, 1 h after occlusion, the cortical norepinephrine and striatal 5-hydroxy-tryptamine levels significantly decreased, and striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid levels markedly increased. In contrast, the levels of histamine and tele-methylhistamine in either brain region gradually increased and the changes became pronounced and statistically significant 6-12 h after induction of ischemia. The striatal histamine and tele-methylhistamine reached levels three- and twofold higher, respectively, than those of the contralateral side. In rats treated with alpha-fluoromethylhistidine 1 h before induction of ischemia, elevation of histamine and tele-methylhistamine was not observed. The elevated histamine level in the ipsilateral straitum at 9 h after occlusion was further significantly increased by the treatment with metoprine, an inhibitor of histamine-N-methyltransferase. These results suggest that the histaminergic activity in the brain is gradually enhanced by cerebral ischemia.
 ...
PMID:Changes in the metabolism of histamine and monoamines after occlusion of the middle cerebral artery in rats. 205 Nov 72

The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity. 224 40

The mechanism by which cocaine produces sudden cardiac death has not been elucidated, but clinical evidence indicates that it may be due to a direct or indirect action on coronary vessels. The present study was designed to compare the responses of the isolated left anterior descending (LAD) coronary artery and femoral artery taken from untreated dogs with the response of these vessels taken from dogs administered cocaine (1 mg/kg i.v.) daily for 4 weeks. The actions of norepinephrine, U-46619 (a thromboxane A2 analog) and serotonin (5-HT) were evaluated. The direct vascular action of cocaine was also determined. Morphology of the blood vessels was evaluated by scanning electron microscopy. Chronic cocaine treatment significantly increased the sensitivity and maximum response of the femoral artery to norepinephrine, U-46619 and 5-HT. The sensitivity of the LAD coronary artery to U-46619 and 5-HT and the maximum response to U-46619 and 5-HT were also enhanced. Vasoconstriction produced by cocaine was not dose dependent and only occurred at high concentrations (10(-5)-10(-4) M). Morphology of the vessels was evaluated by scanning electron microscopy. Femoral arteries from cocaine-treated dogs exhibited loss of endothelial integrity, areas of excessive endothelial cell sloughing and thrombus formation. LAD coronary arteries exhibited only areas of enhanced endothelial cell sloughing. The results of this study indicate that the femoral artery and the LAD coronary artery are more sensitive to endogenous vasoactive substances after chronic cocaine use, which may result in enhanced peripheral vasoconstriction and cardiac ischemia. Morphological results demonstrate femoral arterial thrombosis associated with cocaine use.
 ...
PMID:Chronic cocaine treatment enhances the responsiveness of the left anterior descending coronary artery and the femoral artery to vasoactive substances. 226 7

Cerebral ischemia induced by bilateral common carotid artery occlusion (15 min) with and without release (1 hr) served as a model for comparative regional studies of synaptosomal 3H-5-hydroxytryptamine (3H-5-HT) uptake and release in adult and young gerbils. A decreased uptake and an increased release of 5-HT was observed in the adult after ischemia alone and/or ischemia with reflow. At the same time, 5-HT uptake was not affected except in the cortex and the release was reduced in the young. These findings indicate that the same ischemic insults affect differently the synaptosomal uptake and/or release of 5-HT in adult and young brain.
 ...
PMID:Effect of cerebral ischemia on synaptosomal uptake and release of 3H-5-hydroxytryptamine in adult and young Mongolian gerbils. 233 47

In the hamster cheek pouch, microvascular effects of iloprost at a nonhypotensive dose include vasodilatation at the level of arterioles and venules without changes in microvascular permeability, increased number of perfused capillaries/cm2, prevention of microvascular spasm and capillary ischemia as caused by LTD4, and inhibition of histamine- and 5-HT-induced venular leakage of FITC-dextrane. As regards the effects on basal vessel tone, capillary density, and prevention of LTD4 effects, PGE1 had similar effects as also shown by others in the human cutaneous microcirculation. However, PGE1 did not prevent the microvascular leakage caused by histamine. The Ca2+-antagonist nifedipine, apart from arteriolar vasodilatation, neither increased venular diameter and capillary perfusion nor prevented the effects of LTD4 and histamine. The microvascular actions of iloprost by improvement of tissue perfusion and prevention of mediator-induced tissue edema and vasospasm could contribute to the beneficial effects observed in ischemic diseases.
 ...
PMID:Microvascular effects of iloprost in the hamster cheek pouch. 244 80

Serotonin concentrations and receptor binding characteristics were investigated in rats subjected to total hepatectomy, portacaval shunt (PCS) or sham-operation. The animals were infused for 5 hr with a 10% glucose solution or the same solution enriched with 0.24 M branched-chain amino acids (BCAA). Hepatectomized animals were in grade-two coma at the end of the experiment independent of infusion. Indoleamines in mesencephalon-pons and diencephalon were analyzed by high-pressure liquid chromatography with electrochemical detection. Serotonin receptors (5-HT1 and 5-HT2) were investigated in the cortex and hippocampus by radioligand binding studies using 3H-serotonin for analysis of 5-HT1-receptors and 3H-ketanserin for analysis of 5-HT2-receptors. Concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly increased after hepatectomy compared with controls. Treatment with BCAA significantly decreased 5-HT and 5-HIAA levels in hepatectomized animals. The affinity and the number of binding sites for the 5-HT1 and 5-HT2 receptors were found to be similar in all groups. The present study indicates that PCS for 1 week and the anhepatic state for 5 hr in rats do not influence brain serotonin receptors in contrast to previous studies in pigs with liver ischemia or rabbits with galactosamine-induced liver damage. In addition, infusion of BCAA for 5 hr did not alter the binding characteristics.
 ...
PMID:Serotonin receptors in the brain following total hepatectomy in rats treated with branched-chain amino acids. 247 82

The pathogenesis of the human muscular dystrophies is unknown, and several competing hypotheses have been proposed. The vascular hypothesis states that muscle fibre necrosis occurs in dystrophy as a result of transient muscle ischemia. Although abnormalities of the vascular system may be demonstrated in dystrophy, their role in pathogenesis remains obscure. The responses to serotonin (5-HT) and noradrenaline (NA) were examined in isolated ischiatic artery preparations from normal and genetically dystrophic chickens. The tension generated in response to 5-HT was greater in arteries from normal chickens than in arteries from dystrophic chickens, whereas responses to NA were similar. Analysis of the concentration-response relationships demonstrated that the dystrophic ischiatic artery was less sensitive to 5-HT than was the normal artery, although the sensitivity to NA was similar in both vessels. The results of this study are not consistent with the view that muscle fibre necrosis in avian dystrophy is a consequence of muscle anoxia. These data do demonstrate pharmacological differences between dystrophic avian arteries and arteries from normal chickens, but their presence may represent merely the expression of dystrophy in vascular smooth muscle.
 ...
PMID:Effects of noradrenaline, serotonin, and selected antagonists on the vascular smooth muscle of normal and dystrophic chickens. 294 32

The effects of several concentrations of amines and reducing agents on the activity of creatine (CK) and adenylate (AK) kinases were determined in homogenates of the brain of the rat at 0 and 37 degrees C. The order of decreasing irreversible inhibition of the enzymes was peroxide, 6-hydroxydopamine, dopamine, norepinephrine, 5-hydroxytryptamine. At 37 degrees C, approx. 50% of the activity of creatine kinase was lost in 30 min in the presence of 20 microM dopamine. 5-Hydroxytryptamine was several orders of magnitude less toxic. The action of dopamine was not prevented by inhibition of monoamine oxidase, chelation of metals or the addition of a catalase, indicating that formation of peroxide by monoamine oxidase was not the primary cause of the loss of enzyme. Although auto-oxidation of dopamine to a toxic quinone was considered, the degree of inhibition of creatine kinase was not affected when auto-oxidation was prevented under anaerobic conditions. Glutathione (GSH), present during the incubation, protected the enzymes but could not restore activity after exposure to amine. Concentrations of glutathione above 5 mM and of oxidized glutathione as low as 10 microM inhibited creatine kinase. Ascorbate protected the enzymes even when present at a concentration much less than that of the amine, but ascorbate was itself toxic. The findings indicate that dopamine, at concentrations attained after drug-induced release or ischemia, can be toxic to a metabolic enzyme present in the synaptosomal membrane.
 ...
PMID:Amine-mediated toxicity. The effects of dopamine, norepinephrine, 5-hydroxytryptamine, 6-hydroxydopamine, ascorbate, glutathione and peroxide on the in vitro activities of creatine and adenylate kinases in the brain of the rat. 300 2

Sixty-minute partial ischemia (occlusion of a. cerebri media dextra) had no such marked effect on changes in monoamine levels as observed after longer intervals. In differentiated parts of area S II (area of direct damage) there was a significant increase of NE in g. sylvius ant. and g. coronarius in comparison to sham-operated controls, a significant elevation of 5-HT in g. sylvius ant. and lesser nonsignificant dopamine changes in area S II. An interesting finding was that in comparison with monoamine levels in sham-operated controls there were changes in their levels also in the contralateral hemisphere of animals with experimentally induced ischemia. In the other areas monitored there were no changes. These results from unilateral partial brain ischemia are corroborated by the findings of other authors at total brain ischemia and indicate that shorter intervals of ischemia produce only slight reversible changes in monoamines whereas longer intervals produce their reduction and impaired metabolism.
 ...
PMID:Effect of local ischemia on catecholamine and 5-hydroxytryptamine levels in the dog brain. 366 Nov 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>