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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. 190 37

We occluded the carotid and vertebral arteries of 12 rats for 15 minutes to measure the brain concentrations of choline and acetylcholine and cerebral blood flow at the end of the ischemic period or 15, 30, or 150 minutes after circulation was reestablished. The animals were sacrificed with microwave radiation focused to the head immediately after a brief infusion of [14C]iodoantipyrine with rapid sampling of arterial blood. Brain tissue samples were extracted with ether to separate the tracer, which was subsequently measured by liquid scintillation counting and used to calculate local cerebral blood flow. The aqueous phase was then processed for the measurement of choline and acetylcholine concentrations by gas chromatography/mass spectrometry. The results showed a large increase in tissue choline content and a decrease in tissue acetylcholine content during ischemia. During recirculation, choline levels progressively declined, reaching levels lower than those in four control rats after 150 minutes of recirculation for most brain regions. A reciprocal relation between the brain choline concentration and local cerebral blood flow was found. Acetylcholine levels showed an initial rebound to greater than control during recirculation, with subsequent normalization. Brain acetylcholine concentration was positively correlated with brain choline concentration, provided that cerebral blood flow was greater than 0.3 ml x g-1 x min-1. Because tissue free choline was depleted in most brain regions 150 minutes after transient ischemia, we speculate that prolonged ischemia may produce a greater depletion of tissue free choline with a resulting decline in tissue acetylcholine. This could play an important role in the cognitive deficit associated with vascular dementia.
Stroke 1991 May
PMID:Time-dependent changes in cerebral choline and acetylcholine induced by transient global ischemia in rats. 202 95

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49

The effects of prolonged infusions of ethanol on endothelium-dependent vasorelaxation induced by acetylcholine and adenosine triphosphate (ATP) and on endothelium-independent relaxation induced by papaverine were studied and compared in isolated perfused rat mesenteric artery preparations. Infusion of ethanol over 60 minutes at concentrations of 1.6, 4.7, 6.3, and 7.9 mg/ml caused concentration-related inhibition of norepinephrine-induced vasoconstriction. In preparations infused with 6.3 and 7.9 mg/ml, this effect reached a maximum after 10-20 minutes but had vanished by the end of the infusion; 1 hour after the end of the infusion, the effects of norepinephrine were potentiated by 71% and 108%, respectively. Acetylcholine-induced vasorelaxation (EC50 3.0 ng/ml in controls) was significantly reduced after 6.3 mg/ml ethanol infusion and totally abolished after 7.9 mg/ml ethanol infusion. ATP-induced vasorelaxation (EC50 180 ng/ml in controls) was also abolished after 7.9 mg/ml of ethanol infusion. By contrast, the vasorelaxant effects of papaverine were not affected by 7.9 mg/ml ethanol infusion. Light-microscopic examination revealed that the endothelial cells were present in ethanol-treated and in control mesenteric arterial beds. These observations indicate that ethanol suppresses endothelium-dependent vasorelaxation without apparent removal of the endothelial cells. The compromised relaxant capacity of the endothelium after ethanol and the resultant intensification of the vasoconstrictor response to norepinephrine may contribute to the development of vascular diseases such as hypertension and stroke.
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PMID:Alcohol suppresses endothelium-dependent relaxation in rat mesenteric vascular beds. 278 50

We measured regional cerebral blood flow and acetylcholine and choline concentrations in tissue fragments of normally perfused and ischemic cortical regions from 10 rats. Tissue uptake of [14C]iodoantipyrine was used to indicate regional cerebral blood flow, and gas chromatography-mass spectrometry was used to measure acetylcholine and choline concentrations. Cerebral cortical ischemia was induced by permanent occlusion of the middle cerebral artery, and variables were measured 2.5 or 24 hours later. A close correlation was found between tissue choline concentration and the reciprocal of regional cerebral blood flow. A large increase in tissue choline concentration was observed in the ischemic cortex. Choline production rate was estimated by plotting choline concentration against the reciprocal of regional cerebral blood flow. This rate was independent of choline concentration. Acetylcholine concentration, on the other hand, was constant in ischemic and normally perfused regions, except in the center of the ischemic region 2.5 hours after middle cerebral artery occlusion, where a significant decrease was observed.
Stroke 1989 Nov
PMID:Effects of middle cerebral artery occlusion on cerebral cortex choline and acetylcholine in rats. 281 87

This article surveys the conventional neurotransmitters and modulatory neuropeptides that are found in the cerebral cortex and attempts to place them into the perspective of both intracortical circuitry and cortical disease. The distribution of these substances is related, where possible, to particular types of cortical neuron or to afferent or efferent fibers. Their physiological actions, where known, on cortical neurons are surveyed, and their potential roles in disease states such as the dementias, epilepsy, and stroke are assessed. Conventional transmitters that occur in afferent fibers to the cortex from brain-stem and basal forebrain sites are: serotonin, noradrenaline, dopamine, and acetylcholine. All of these except dopamine are distributed to all cortical areas: dopamine is distributed to frontal and cingulate areas only. The transmitter in thalamic afferent systems is unknown. Gamma aminobutyric acid (GABA) is the transmitter used by the majority of cortical interneurons and has a profound effect upon the shaping of receptive field properties. The vast majority of the known cortical peptides are found in GABAergic neurons, and the possibility exists that they may act as trophic substances for other neurons. Levels of certain neuropeptides decline in cases of dementia of cortical origin. Acetylcholine is the only other known transmitter of cortical neurons. It, too, is contained in neurons that also contain a neuropeptide. The transmitter(s) used by excitatory cortical interneurons and by the efferent pyramidal cells is unknown, but it may be glutamate or aspartate. It is possible that excitotoxins released in anoxic disease of the cortex may produce damage by acting on receptors for these or related transmitter agents.
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PMID:Neurotransmitters in the cerebral cortex. 287 11

The goal of this study was to determine whether endothelium-dependent responses are impaired in the cerebral microcirculation of stroke-prone spontaneously hypertensive rats (SHRSP). We measured diameters of cerebral arterioles using intravital microscopy in normotensive rats (WKY) and SHRSP (6-8 mo old). Cerebral vasodilator responses to superfusion with adenosine, which is an endothelium-independent agonist, were similar in WKY and SHRSP. In contrast, cerebral vasodilator responses to superfusion with endothelium-dependent agonists were profoundly impaired in SHRSP. Acetylcholine (10(-4) M) increased pial arteriolar diameter 23 +/- 2% (means +/- SE) in WKY and did not change arteriolar diameter in SHRSP (-2 +/- 3%, P less than 0.05 vs. WKY). Serotonin (10(-5) M) increased pial arteriolar diameter 23 +/- 1% in WKY and, in contrast, reduced diameter 11 +/- 1% in SHRSP (P less than 0.05 vs. WKY). Nitroglycerin and acetylcholine produce vasodilatation by activation of guanosine 3',5'-cyclic monophosphate (cGMP). Nitroglycerin was used to determine whether impaired responses of cerebral arterioles in SHRSP were related to altered cGMP activity. We found similar dilatation of cerebral arterioles in WKY and SHRSP in response to nitroglycerin. Thus impaired endothelium-dependent dilatation in SHRSP is not related to alteration of cGMP activity. We speculate that impairment of cerebral vasodilator responses to endothelium-dependent agonists, including vasoactive substances released by platelets, may predispose SHRSP to cerebral ischemia.
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PMID:Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension. 312 90

To determine whether extraluminal or intraluminal hemoglobin inhibits endothelium-dependent relaxation, we measured the vascular responsiveness of rabbit basilar artery in an in vitro perfusion system and we performed immunohistochemical staining for hemoglobin. In the in vitro study, we applied agents from either the intraluminal or the extraluminal side of excised basilar arteries. KCl-induced contraction was the same with either application. Acetylcholine-induced maximal relaxations were 57.6 +/- 8.5% of the contraction induced by 10(-5) M 5-hydroxytryptamine for control, 3.3 +/- 0.3% for intraluminal, and 34.9 +/- 8.6% for extraluminal applications. Adenosine triphosphate-induced maximal relaxations were 64.2 +/- 4.1% of the contraction induced by 10(-5) M 5-hydroxytryptamine for control, 26.9 +/- 3.8% for intraluminal, and 42.2 +/- 6.0% for extraluminal applications. Hemoglobin's inhibition of acetylcholine- and adenosine triphosphate-induced relaxation was significantly greater with intraluminal than with extraluminal application (p less than 0.05). The immunohistochemical study revealed hemoglobin in the outer layer of the smooth muscle and in the adventitia when 10(-5) M hemoglobin was applied extraluminally for 5 minutes, whereas hemoglobin was observed on the surface of the endothelial cells after intraluminal application. Our findings suggest that hemoglobin inhibits acetylcholine- or adenosine triphosphate-induced relaxation by binding to endothelium-derived relaxing factor (EDRF) and by inhibiting production of EDRF. Hemoglobin's inhibitory effect on endothelium-dependent relaxation may be important in the pathogenesis of vasospasm after subarachnoid hemorrhage.
Stroke 1988 Dec
PMID:Comparison of intraluminal and extraluminal inhibitory effects of hemoglobin on endothelium-dependent relaxation of rabbit basilar artery. 326 26

1. The effects of sodium nitroprusside, acetylcholine and bradykinin on cardiac output and its distribution were studied in the anaesthetized, vagotomised rat preparation by use of 113Sn-labelled microspheres. 2. All three vasodilators lowered peripheral arterial blood pressure, but only bradykinin significantly reduced total peripheral resistance without reducing cardiac output. Bradykinin caused tachycardia, but this was offset by a reduction in stroke volume. These effects of bradykinin were not altered by indomethacin (4 mg kg-1). Acetylcholine and sodium nitroprusside both caused significant (P less than 0.05) reductions in stroke volume and cardiac output. 3. Bradykinin reduced vascular resistance in the liver, stomach, small intestine, large intestine, pancreas/mesentery, epididimides, skeletal muscle and fat. These responses were not affected by indomethacin, whereas, the reduction in vascular resistance in the brain induced by bradykinin was abolished by indomethacin. 4. Acetylcholine caused a reduction in renal vascular resistance, where bradykinin had no effect. However, acetylcholine did not cause any haemodynamic changes in the bradykinin-sensitive intestinal vasculature. 5. Acetylcholine caused vasoconstriction in the coronary and epididymal vasculature. Bradykinin in the presence of indomethacin induced vasoconstriction in the skin. 6. In conclusion, the data show that, with the possible exception of the brain and the skin, the vasodilator actions of bradykinin can adequately be transduced (presumably by endothelium-derived relaxing factor, EDRF) in the absence of prostacyclin synthesis. Additionally, these results indicate that the vasculature of the stomach, pancreas/mesentery, epididimides and skeletal muscle are equally sensitive to both acetylcholine and bradykinin, whereas the kidneys showed selectivity towards acetylcholine and the intestines towards bradykinin. These results may indicate differential receptor populations.
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PMID:The effects of endothelium-dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside. 326 37

Choline acetyltransferase (ChAT), the enzyme responsible for the formation of ACh from choline and acetyl-coenzyme A, is a marker of cholinergic function and is significantly depressed in the brains of Alzheimer patients. It has been shown that omental tissue contains several neuroactive substances and causes revascularization when placed upon the brain of stroke patients. In this study, it was demonstrated that omental tissue exhibits specific ChAT activity. This activity was choline-dependent, inhibited by N-ethylmaleimide (a known ChAT inhibitor), and was characterized by kinetic parameters consistent with values for the neuronal enzyme. It is suggested that omental placement to the brain together with oral choline administration might prove to be useful for increasing ACh synthesis in Alzheimer's disease.
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PMID:Choline acetyltransferase activity in omental tissue. 326 42


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