Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute hypertension induced by adrenergic agents opens up the blood-CSF barrier (choroid plexus) to nonelectrolyte and protein tracers. Sprague-Dawley adult rats anesthetized with ketamine were given an intravenous bolus of either epinephrine (10 micrograms/kg), phenylephrine (100 micrograms/kg), isoproterenol (10 micrograms/kg), or D,L-amphetamine (2 mg/kg). Tracers were injected simultaneously with test agents, and the animals killed 10 min later. Epinephrine raised MABP by 57 mm Hg, to a peak pressure of 160 mm Hg; and it increased the volume of distribution (Vd) of urea, mannitol, and 125I-bovine serum albumin in CSF by 1.5-, 2.7-, and 30-fold, respectively. There was enhanced uptake by lateral and fourth ventricle choroid plexuses, cerebral cortex, cerebellum, medulla, and thalamus. Phenylephrine also elevated MABP to 160 mm Hg, but it increased permeation of tracers into CSF (and several brain regions) to a lesser extent than epinephrine, attributable to protective vasoconstriction associated with alpha-agonist activity. Ratio analysis of Vd data provides evidence that augmented permeation of nonelectrolyte tracers in acute hypertension occurs predominantly by diffusion rather than vesicular transport. It is postulated that elevated MABP distends the central cores of choroid plexus villi and cerebral capillaries, with resultant stretching and opening of tight junctions in both barrier systems; with less hindrance to diffusion, urea and mannitol are cleared at rates closer to free diffusion. Neither isoproterenol (decreased MABP by 40 mm Hg) nor amphetamine (did not alter MABP) significantly opened the choroid plexus or blood-brain barrier to tracers.
J Cereb Blood Flow Metab 1985 Sep
PMID:Adrenergic-induced enhancement of brain barrier system permeability to small nonelectrolytes: choroid plexus versus cerebral capillaries. 392 38

Levels of energy metabolites were measured in forebrain regions in fasted rats subjected to 4-h recirculation after 1 h of either incomplete or complete ischemia. Both models of ischemia were produced by a procedure combining bilateral common carotid artery occlusion, systemic hypotension, and CSF pressure elevation; the degree of intracranial hypertension was varied to produce incomplete and complete ischemia. Levels of brain lactate at the end of ischemia ranged from 16 to 19 mmol/kg in incomplete ischemia and from 11 to 13 mmol/kg in complete ischemia. Energy metabolism recovered evenly in the neocortical and subcortical regions with recirculation after incomplete ischemia. The metabolic recovery in the cerebral cortex after complete ischemia was similar to that observed after incomplete ischemia; however, recovery in the subcortical regions after complete ischemia was less extensive, NADH fluorescence remained high, and there was a fall in total creatine. Intracellular pH in the dorsal thalamus was more alkalotic after complete than incomplete ischemia. Thus, in the absence of profound tissue lactic acidosis, residual CBF during prolonged ischemia helps postischemic restitution of brain energy metabolism in subcortical regions. The pattern of poor recovery in these regions after complete ischemia suggests inadequate reperfusion. The decreased total creatine and the severe tissue alkalosis may be biochemical markers of advanced tissue injury during reflow.
J Cereb Blood Flow Metab 1985 Dec
PMID:Regional brain energy metabolism after complete versus incomplete ischemia in the rat in the absence of severe lactic acidosis. 405 23

In normal brain, the blood-brain barrier (BBB) is highly impermeable to K+ cations, their transport being controlled by ATPases situated in the endothelial cell membranes. 82Rb+ is a positron-emitting analogue of K+ with a half-life of 75 s. Using a steady-state model and positron emission tomography, quantitative extraction data for 82Rb+ transport across the BBB have been obtained both in normal human subjects and in a variety of conditions of cerebral pathology. A mean cerebral Rb extraction of 2.1% was found for normal subjects, corresponding to a mean value of 1.1 x 10(-6) cm s-1 for 82Rb+ cation permeability across the BBB. No increase in cerebral Rb extraction was observed for patients with diffusely raised intracranial pressure secondary to obstructive hydrocephalus and benign intracranial hypertension, or for patients with multiple sclerosis or cerebral systemic lupus erythematosus. Cerebral tumours that were enhanced on computed tomography scanning showed a significant increase in local Rb uptake. No correlation between tumour size, or grade of glioma, and tumour Rb extraction was found. Nonenhancing tumours showed no increase in local Rb extraction, and regions of perifocal tumour oedema also had Rb extraction values in the normal range. It is concluded that increased Rb extraction occurs only where tight junction integrity in the BBB breaks down locally, that is, in the microcirculation of enhancing tumours but not in that of perifocal regions of tumour oedema or nonenhancing tumours.
J Cereb Blood Flow Metab 1984 Dec
PMID:Quantitative measurement of blood-brain barrier permeability using rubidium-82 and positron emission tomography. 633 92

Although it is known that hypercarbia increases and benzodiazepines decrease cerebral blood flow (CBF), the effects of benzodiazepines on CBF responsiveness to CO2 are not well documented. The influence on CBF and CBF-CO2 sensitivity of placebo or midazolam, which is a new water-soluble benzodiazepine, was measured in eight healthy volunteers using the noninvasive 133Xe inhalation method for CBF determination. Under normocarbia, midazolam decreased CBF from 40.6 +/- 3.2 to 27.0 +/- 5.0 ml 100 g-1 min-1 (means +/- SD). At a later session under hypercarbia, CBF was 58.8 +/- 4.4 ml 100 g-1 min-1 after administration of placebo, and 49.1 +/- 10.2 ml 100 g-1 min-1 after midazolam. The mean of the slopes correlating PaCO2 and CBF was significantly steeper with midazolam (2.5 +/- 1.2 ml 100 g-1 min-1 mm Hg-1) than with placebo (1.5 +/- 0.4 ml 100 g-1 min-1 mm Hg-1). Our results suggest that midazolam may be a safe agent to use in patients with intracranial hypertension, since it decreases CBF and thus cerebral blood volume; however, it should be administered with caution in nonventilated patients with increased intracranial pressure, since its beneficial effects on cerebrovascular tone can be readily counteracted by the increase in arterial CO2 tension induced by this drug.
J Cereb Blood Flow Metab 1983 Jun
PMID:Effects of midazolam on cerebral hemodynamics and cerebral vasomotor responsiveness to carbon dioxide. 640 14

The question of the significance of the cerebrovascular effects of stressful situations in animals is still controversial. In the present article, an experimental model of immobilization stress in the rabbit is described, and its specificity in relation to arterial blood pressure and PaCO2 is investigated. CBF was measured with the multiregional tissue sampling technique using [14C]-ethanol as tracer. After dissipation of althesin anesthesia, the stress reaction was elicited by tactile abdominal stimuli. The response was evidenced by an instantaneous acute hypertension (+33.8% during the CBF measurement period). Within the first minute of the reaction, the CBF was significantly increased in all nine structures studied by 39% (caudate nucleus) to 82% (parieto-temporal cortex). The study of the influence of arterial blood pressure and the PaCO2 on CBF showed that cerebrovascular autoregulation and CO2 sensitivity were differently affected in the various structures during the stress reaction. However, the stress response of the brain circulation could not be entirely ascribed to one or both of these two systemic factors, thus suggesting the contribution of a local intrinsic activation. The model presented here could be useful for long-term studies of cerebrovascular repercussions of repeated acute hypertensions of a stressful nature.
J Cereb Blood Flow Metab 1984 Sep
PMID:Significance of the cerebrovascular effects of immobilization stress in the rabbit. 643 9

Local rates of glucose utilization in the superior cervical, cardiac, and coeliac ganglia were measured by means of the autoradiographic 2-deoxy-D-[14C]glucose method in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), 32-34, 46-48, and 78-87 days old. Brain glucose utilization was examined in 78-87-day-old SHR and WKY. At 32-34 days (at which time mean arterial blood pressure was normal and similar in both groups of rats), the rates of glucose utilization of all three sympathetic ganglia were the same in both groups. At 46-48 days, despite the fact that blood pressure had risen significantly in SHR (mean +/- SEM, 136 +/- 3 mm Hg, n = 5, compared to 113 +/- 3 mm Hg, n = 5, in the control WKY), glucose utilization was decreased in the cardiac and coeliac ganglia but not in the superior cervical ganglia of the SHR. At 78-87 days, glucose utilization was reduced in all the sympathetic ganglia of the hypertensive rats. These results suggest that the sympathetic system is less active in SHR and indicate that hyperactivity of the sympathetic nervous system is not part of the mechanism of the hypertension. Of 44 structures examined in the central nervous system, only the external cuneate, vestibular, and fastigial nuclei of the SHR exhibited increased rates of glucose utilization, and no changes were found in any of the other structures. These increases are probably not related to the origin or maintenance of the hypertension, inasmuch as lesioning of the vestibular or fastigial nuclei did not decrease blood pressure in the SHR.
J Cereb Blood Flow Metab 1983 Dec
PMID:Metabolic mapping in the sympathetic ganglia and brain of the spontaneously hypertensive rat. 663 Mar 15

Interrelationship between the breakdown of the blood-brain barrier (BBB) to Evans blue and elevations in the regional cerebral blood flow (rCBF) was studied in rabbits subjected to adrenaline- or metaraminol-induced systemic hypertension and also in bicuculline-induced seizures. The rCBF was assessed in small samples from various regions of the brain with the use of [3H]nicotine, and the permeability of the BBB was evaluated with an Evans blue tracer. In acute hypertension, Evans blue extravasations were observed in the occipital cortex and sometimes in the superior colliculus, i.e., the regions which also showed the highest elevations in rCBF. The breakdown of the BBB in acute hypertension was clearly related to the rate of mean arterial blood pressure rise, being much less pronounced in the metaraminol group, which showed a much slower blood pressure elevation rate. In bicuculline-induced seizures, there was no evident correlation between the amplitude of rCBF elevations and Evans blue extravasations. Preservation of BBB integrity was observed in areas showing high elevations in the rCBF.
J Cereb Blood Flow Metab 1984 Mar
PMID:Regional changes in cerebral blood flow and blood-brain barrier permeability during epileptiform seizures and in acute hypertension in rabbits. 669 17

The effects of stepwise arterial hypotension (MABP: 80, 60, 40 mm Hg) and moderate arterial hypo- and hypertension (MABP: 80, 150-160 mm Hg) on cerebrocortical vascular volume and NAD/NADH redox state were studied in anaesthetized cats. The vascular volume and NADH fluorescence measurements were performed on closed skull preparations using a microscope fluororeflectometer. To determine the possible role of adrenergic alpha-receptors in the autoregulatory adjustment of cerebrocortical vascular volume, some of the animals were pretreated with intra-arterially infused phenoxybenzamine (1 mg/kg). It was found that longlasting stepwise arterial hypotension leads to a gradual increase in cerebrocortical vascular volume and NADH fluorescence. Though the cerebrocortical arteries dilatated considerably at 80 mm Hg, sustained for 30 min, the NAD/NADH redox state failed to be reoxidized but was shifted to a more reduced state. This finding suggests that some factor other than tissue hypoxia is responsible for the dilatation of cerebrocortical vessels during moderate arterial hypotension. When the arterial blood pressure was restored following stepwise arterial hypotension, the cerebrocortical vascular volume did not decrease and the NAD/NADH redox state remained reduced, showing that the autoregulatory capability of the vessels was lost and the tissue metabolism was irreversibly altered. During a 5-min duration of moderate arterial hypo- and hypertension, biphasic changes were obtained in cerebrocortical vascular volume while the NAD/NADH redox state was shifted to a more reduced and oxidized state. Since the dilatation and the constriction of the cerebrocortical vessels during arterial hypo- and hypertension lagged by 40-80 s behind the redox state alterations, it is suggested that the myogenic mechanism has a minor role in CBF autoregulation. Phenoxybenzamine (PBZ) dilatated the cerebrocortical vessels, indicating the existence of an active alpha-receptor-mediated vasoconstrictory tone. Since the extent of autoregulatory vascular volume changes was not affected by PBZ pretreatment, the involvement of adrenergic alpha-receptors in the autoregulation of CBF can be excluded, at least for cats.
J Cereb Blood Flow Metab 1982
PMID:Effect of acute arterial hypo- and hypertension on cerebrocortical NAD/NADH redox state and vascular volume. 707 33

The effect of chronic hypertension on cerebral blood flow (CBF) was studied in anaesthetised rats. CBF was measured with the intracarotid 133Xe injection method. Rats with spontaneous and renal hypertension were compared with normotensive controls. The lower limit of autoregulation was determined during controlled haemorrhage. In the normotensive rats, CBF remained constant until mean arterial pressure (MAP) had decreased to the range of 50-69 mm Hg. Thereafter, CBF decreased with each further decrease in MAP. In both types of hypertensive rats, CBF remained constant until MAP had decreased to the range of 70-89 mm Hg. Thus, a 20-mm Hg shift of the lower limit of CBF autoregulation was found in both spontaneous and renal hypertensive rats. A neuropathological study revealed ischaemic brains lesions in half of the hypertensive rats following hypotension, whereas only a single lesion was found in one of six normotensive rats. No ischaemic brain lesions were found in a control study in which CBF was shown to be stable over a 21/2-h period. In conclusion, hypertensive rats showed a shift of the lower limit of CBF autoregulation as well as an increased susceptibility to ischaemic brain damage during hypotension. These findings presumably reflect hypertensive structural changes in the cerebral circulation.
J Cereb Blood Flow Metab 1982 Sep
PMID:Cerebral blood flow in rats with renal and spontaneous hypertension: resetting of the lower limit of autoregulation. 709 59

Acute hyperammonemia causes cerebral edema, elevated intracranial pressure and loss of cerebral blood flow (CBF) responsivity to CO2. Inhibition of glutamine synthetase prevents these abnormalities. If the loss of CO2 responsivity is secondary to the mechanical effects of edema, one would anticipate loss of responsivity to other physiological stimuli, such as hypoxia and changes in mean arterial blood pressure (MABP). To test this possibility, pentobarbital-anesthetized rats were subjected to either hypoxic hypoxia (PaO2 approximately 30 mm Hg), hemorrhagic hypotension (MABP approximately 70 and 50 mm Hg), or phenylephrine-induced hypertension (MABP approximately 125 and 145 mm Hg). CBF was measured with radiolabeled microspheres. Experimental groups received intravenous ammonium acetate (approximately 50 mumol min-1 kg-1) for 6 h to increase plasma ammonia to 500-600 microM. Control groups received sodium acetate plus HCl to prevent metabolic alkalosis. The increase in CBF during 10 min of hypoxia after 6 h of ammonium acetate infusion (84 +/- 19 to 259 +/- 52 ml min-1 100 g-1) was similar to that after sodium acetate infusion (105 +/- 20 to 265 +/- 76 ml min-1 100 g-1). Cortical glutamine concentration was elevated equivalently in hyperammonemic rats subjected to normoxia only or to 10 min of hypoxia. With severe hypotension, CBF was unchanged in both the ammonium (80 +/- 20 to 76 +/- 24 ml min-1 100 g-1) and the sodium (80 +/- 14 to 73 +/- 16 ml min-1 100 g-1) acetate groups. With moderate hypertension, CBF was unchanged. With the most severe hypertension, significant increases in CBF occurred in both groups, but there was no difference between groups. We conclude that hypoxic and autoregulatory responses are intact during acute hyperammonemia. The previously observed loss of CO2 responsivity is not the result of a generalized vasoparalysis to all physiological stimuli.
J Cereb Blood Flow Metab 1995 Sep
PMID:Preservation of cerebral blood flow responses to hypoxia and arterial pressure alterations in hyperammonemic rats. 767 76


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