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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment with the alpha 2-adrenergic antagonist idazoxan (IDA) can provide protection from global cerebral ischemia. However, IDA also recognizes another class of receptors, termed imidazole (IM) receptors, which differ from alpha 2-adrenergic receptors and are responsible for the hypotensive actions of some centrally acting agents such as the oxazole rilmenidine (RIL). We therefore sought to determine whether RIL, an agent highly selective for IM receptors, offered protection from focal cerebral ischemia elicited in rat by ligation of the middle cerebral artery (MCA). We compared the effects of RIL with the effects of IDA and the selective non-IM alpha 2-antagonist SKF 86466 (SKF). In addition, we examined whether the neuroprotective effects of RIL and IDA could be attributed to changes in local CBF (LCBF). The MCA was occluded and animals either received immediate administration of drug while arterial pressure was maintained for 1 h or had local CBF increased to 200% of control for 1 h by hypercapnia or hypertension. RIL elicited a significant dose-dependent preservation of tissue to 33% of control at optimal dose (0.75 mg/kg). IDA (3 mg/kg) significantly reduced the size of ischemic infarction by 22%. In contrast, SKF (15 mg/kg) as well as doubling of LCBF did not preserve ischemic tissue. We conclude that both RIL and IDA can reduce focal ischemic infarction but that the mechanism does not appear secondary to antagonism of alpha 2-adrenergic receptors or elevation of LCBF. Occupation of IM receptors, either in the ischemic zone or at remote brain sites, may be responsible for neuroprotection of RIL and IDA.
J Cereb Blood Flow Metab 1992 Jan
PMID:Reduction in focal cerebral ischemia by agents acting at imidazole receptors. 134 58

Layer II pyramidal neurons in retrosplenial granular cortex (Rg) give rise to apical dendrites that bundle together tightly in layer Ic and Ib and spread out in layer Ia, where they arborize extensively. These dendritic bundles in Rg become disorganized in very old rats. Since hypertensive rats appear to age more rapidly than normotensive rats, we tested the hypothesis that the disorganization of the dendritic bundles in layer I of Rg is present at a much earlier age in hypertensive rats [spontaneously hypertensive rats (SHR)] compared to normotensive rats [Sprague-Dawley rats (SD)]. Further, we tested the hypothesis that long-term, antihypertensive drug treatment (captopril) prevents or attenuates the breakdown of the dendritic bundles in Rg of SHR. The retrograde tracer Fluorogold was injected into Rg to document the morphology of the apical dendrites of the layer II Rg neurons. In 4-month-old SD and SHR, most densely labeled layer II neurons have labeled apical dendrites that are confined to the dendritic bundles in layer Ib and Ic, and these dendrites arborize extensively only in layer Ia of Rg. In 14-month-old SD this pattern is preserved, but in contrast, in 14-month-old SHR most of the labeled apical dendrites lie outside the bundles, and less than half these dendrites reach layer Ia. Chronic antihypertensive therapy significantly attenuates this disorganization in 14-month-old SHR. These data indicate that in SHR, the layer II neurons in Rg are highly vulnerable to the combined effects of hypertension and aging, and the results suggest that hypertension is a primary contributor to these structural alterations.
Cereb Cortex
PMID:Early breakdown of dendritic bundles in the retrosplenial granular cortex of hypertensive rats: prevention by antihypertensive therapy. 147 25

The effect of phenylephrine-induced hypertension on CBF was investigated after 120 min of middle cerebral artery occlusion in rats. Blood pressure was manipulated by one of the following schedules during a 90-min period of reperfusion: 90/NORM, 90 min of normotensive reperfusion; 90/HTN, 90 min of hypertensive reperfusion (MABP increased by 30 mm Hg); or 15/HTN, the 90-min period of reperfusion was divided into 30 min of normotension, followed by 15 min of hypertension and 45 min of normotension. At the end of reperfusion, 100 microCi kg-1 of [14C]iodoantipyrine was given and an autoradiographic analysis of CBF performed. In the coronal brain section at the center of middle cerebral artery distribution, the area (percentage of hemisphere, mean +/- SD) with a CBF of 0-20 or 21-40 ml 100 g-1 min-1 was less (p less than 0.05) in the 15/HTN group (1 +/- 2 and 5 +/- 3%, respectively) versus the 90/HTN group (12 +/- 4 and 10 +/- 4%), which was in turn less than in the 90/NORM group (18 +/- 5 and 22 +/- 6%). These data are consistent with the hypothesis that during reperfusion a short interval of hypertension effectively augments CBF via an abrupt opening of collapsed vessels and that a more sustained interval of hypertension conveys no added benefit.
J Cereb Blood Flow Metab 1992 Jan
PMID:Focal cerebral ischemia in rats: effects of induced hypertension, during reperfusion, on CBF. 172 43

Recent studies have suggested that under certain conditions, inhalation of stable xenon can cause an increase in CBF or intracranial pressure (ICP). We reviewed the ICP changes that occurred during 48 stable xenon/CT CBF studies in 23 comatose head-injured patients to determine if the concentration (32%) and duration of inhalation (4.5 min) of stable xenon we used caused an increase in ICP. In the group as a whole, there was no significant difference between the mean ICP at the start of xenon inhalation and the mean ICP immediately after completion of the studies. An increase in ICP also was not found in subgroups with low, normal, or high global CBF, or groups with or without intracranial hypertension. Changes in ICP that occurred during individual studies usually were related to corresponding changes in the arterial pCO2 (p less than 0.0001, Pearson's correlation test). Our data suggest that 32% stable xenon administered for 4.5 min does not cause a significant increase in ICP during xenon/CT CBF studies.
J Cereb Blood Flow Metab 1991 Mar
PMID:The effect of stable xenon on ICP. 199 7

Laser-Doppler flowmetry was used to continuously monitor cortical CBF during electrical stimulation of the fastigial nucleus (FN). Rats were anesthetized with isoflurane (0.75-5%), paralyzed, and artificially ventilated. The LDF probe was placed over a target region of the parietal cortex through a burr hole. The hypertension associated with FN stimulation was prevented by spinal cord transection at C1 with arterial pressure maintained by i.v. infusion of phenylephrine. After cord transection, CBF changed linearly with changes in arterial pco2 (r = 0.93; n = 23). FN stimulation (50-100 microA, 50 Hz, 1 s on/1 s off) produced sustained increases in CBF that developed slowly, reaching 50% of maximum within 24 +/- 1 s of stimulation (n = 17). After stimulation, CBF returned to baseline gradually within a time period (84-540 s) proportional to the duration of the stimulation (r = 0.93; n = 15). The CBF response was stimulus frequency and intensity dependent, was elicited only from restricted sites in FN, and was abolished by atropine (1 mg/kg, i.v.) or pentobarbital (30 mg/kg, i.v.). The slow temporal profile of the cerebrovasodilation is compatible with the hypothesis that in cerebral cortex local neurons mediate the vasodilation by interstitial release of vasoactive agents rather than by a direct action of neural processes on blood vessels. LDF is an effective technique for monitoring phasic change in CBF and may be useful in studies of the intrinsic neurogenic control of the cerebral circulation.
J Cereb Blood Flow Metab 1990 Sep
PMID:Continuous monitoring of cerebrocortical blood flow during stimulation of the cerebellar fastigial nucleus: a study by laser-Doppler flowmetry. 211 16

We previously found mild hypothermia (34-36 degrees C), induced before cardiac arrest, to improve neurologic outcome. In this study we used a reproducible dog model to evaluate mild hypothermia by head cooling during arrest, continued with systemic cooling (34 degrees C) during recirculation and for 1 h after arrest. In four groups of dogs, ventricular fibrillation (no flow) of 12.5 min at 37.5 degrees C was reversed with cardiopulmonary bypass and defibrillation in less than or equal to 5 min, and followed by controlled ventilation to 20 h and intensive care to 96 h. In Study A we resuscitated with normotension and normal hematocrit; Control Group A-I (n = 12) was maintained normothermic, while Treatment Group A-II (n = 10) was treated with hypothermia. In Study B we resuscitated with hypertension and hemodilution. Control Group B-I (n = 12) was maintained normothermic (6 of 12 were not hemodiluted), while Treatment Group B-II (n = 10) was treated with hypothermia. Best overall performance categories (OPCs) achieved between 24 and 96 h postarrest were in Group A-I: OPC 1 (normal) in 0 of 12 dogs, OPC 2 (moderate disability) in 2, OPC 3 (severe disability) in 7, and OPC 4 (coma) in 3 dogs. In Group A-II, OPC 1 was achieved in 5 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.001), OPC 3 in 1, and OPC 4 in 0 dogs. In Group B-I, OPC 1 was achieved in 0 of 12 dogs, OPC 2 in 6, OPC 3 in 5, and OPC 4 in 1 dog. In Group B-II, OPC 1 was achieved in 6 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.05), and OPC 3 or 4 in 0 dogs. Mean neurologic deficit and brain histopathologic damage scores showed similar significant group differences. Morphologic myocardial damage scores were the same in all four groups. We conclude that mild brain cooling during and after insult improves neurologic outcome after cardiac arrest.
J Cereb Blood Flow Metab 1990 Jan
PMID:Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. 229 37

The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.
J Cereb Blood Flow Metab 1990 May
PMID:Autoregulation of cerebral blood flow in experimental focal brain ischemia. 232 21

Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined. A small and variable infarcted volume was seen in Wistar-Kyoto rats; Sprague-Dawley rats had a relatively large, but still variable, infarcted volume. Of the normotensive rat strains, the most reproducible volume of infarcted tissue was seen in Fischer-344 rats; also the absolute value of the infarcted volume did not vary from one series to another in this strain. Chronic arterial hypertension, studied in both normal and stroke-prone spontaneously hypertensive rats, was associated with significantly larger infarction volumes. Age does not change the volume of necrosis: Fischer-344 rats were studied at 3, 9, and 20 months of age, and no significant differences were noted between these ages. Experimental diabetes was induced by the administration of streptozotocin 3 days prior to middle cerebral artery occlusion. Severe hyperglycemia (greater than 400 mg/dl) was associated with a considerably increased volume of infarction. The variability of the resultant lesion is high in the most commonly studied strains, but our results suggest that, for studies in normotensive rats, the use of the Fischer-344 strain produces a standardized and repeatable infarction that may be significantly modified by experimental interventions. Age is not a factor that affects the occlusion-induced infarction; in contrast, both chronic arterial hypertension and experimental diabetes aggravate the histological consequences of middle cerebral artery occlusion in the rat. We conclude that quantitative histological evaluation of infarct size allows a meaningful assessment of the gravity of focal cerebral ischemia.
J Cereb Blood Flow Metab 1988 Aug
PMID:The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age. 296 87

The brain uptake of phenobarbital during prolonged status epilepticus (3 h) was studied in paralyzed, ventilated sheep. The first 30 min of status epilepticus was characterized by systemic hypertension, increased CBF, increased peripheral vascular resistance, a fall in brain pH, and an elevation in brain lactate concentrations. Subsequently, hemodynamic factors normalized and brain acidosis persisted. Phenobarbital administered during the early phase of status epilepticus produced higher levels of brain phenobarbital concentration, which was greatest at the earliest sample time (5 min following infusion), compared to nonseizure controls. This elevation persisted for the first 3 h following the infusion. Phenobarbital administration during the established phase of status epilepticus, when systemic blood pressure, peripheral vascular resistance, and CBF had returned to preseizure values, resulted in attenuated brain phenobarbital uptake not different from controls for the first 30 min. These results are explained by disruption of the blood-brain barrier to phenobarbital during the early (hypertensive) phase of status epilepticus.
J Cereb Blood Flow Metab 1987 Dec
PMID:Brain phenobarbital uptake during prolonged status epilepticus. 369 34

Blood-brain barrier (BBB) alterations following acute hypertension were studied in rats, employing as tracers in each animal both horseradish peroxidase (HRP) (MW 40,000) and [14C]alpha-aminoisobutyric acid ([14C]AIB) (MW 104). Eighteen animals were subjected to acute hypertension induced by the intravenous infusion of norepinephrine bitartrate (NE) (Levophed). Five animals injected with both tracers but not infused with NE served as controls. The brain of each animal was serially sectioned with adjacent sections processed either for macroautoradiography or for light microscopic visualization of HRP reaction product via histochemical reaction with tetramethylbenzidine. Quantitative blood-to-brain transfer constants for AIB were determined in each of 14 brain regions. Qualitative comparisons were also made between the AIB and HRP blood-to-brain extravasation patterns in each group. Acute hypertension increased cerebrovascular permeability to both AIB and HRP in most animals. Topographically, the sites of the most highly elevated AIB transfer corresponded with sites of HRP extravasation. Conversely, all sites of protein passage corresponded spatially to sites of elevated AIB transfer. Brain regions commonly showing increased permeability to both tracers included the cerebral cortices, corpus callosum, and thalamus. Importantly, some brain regions showed elevated AIB transfer constants where protein extravasation was absent. These regions included the caudate-putamen, hippocampus, basal forebrain, and cerebellum. These observations suggest that following acute hypertension, alterations in BBB permeability are not limited to vascular segments allowing protein extravasation.
J Cereb Blood Flow Metab 1986 Aug
PMID:Examination of the blood-to-brain transfer of alpha-aminoisobutyric acid and horseradish peroxidase: regional alterations in blood-brain barrier function following acute hypertension. 373 5


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