The Effects of Hypertonic Urea on the Blood-Brain Barrier and on the Glucose Transport in the Brain

Spatz, Maria; Rap, Z. M.; Rapoport, Stanley I.; Klatzo, Igor

doi:10.1007/978-3-642-65448-0_3

Cited by 15 publications

(6 citation statements)

References 17 publications

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“…Other studies have indicated that the lumen of the microvessels remain patent, 21 and we have shown that another enzyme thought to be associated with the plasma membrane of the endothelial cell, lipoprotein lipase, was released from intact microvessels by heparin, reflecting an interaction known to occur in vivo when heparin interacts with the luminal surface of the microvasculature. "…”

Section: Figure 6 Angiotensin-converting Enzyme Activity In Intact MImentioning

confidence: 64%

Properties of angiotensin-converting enzyme in intact cerebral microvessels.

Brecher¹,

Tercyak²,

Chobanian³

1981

Hypertension

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SUMMARY Angiotensin-convertlng enzyme (ACE) was studied in preparations of microvessels isolated from rabbit cerebral cortex. Activity was determined by measuring the degradation of hippuryl-histidyl-leucine (Hip-His-Leu) by the intact microvessels in a physiological salt solution at pH 7.4. ACE activity was dependent on both substrate and chloride ion concentration and was inhibited by captopril in a manner similar to that observed previously with tissue homogenates. Angiotensin I was rapidly degraded by the Intact microvessels, even in the presence of 10~*M captopril. An advantage of the methodology employed was the ability to pretreat the microvessels and then assess the effect of pretreatment by transfer to a postincubation assay system. Pretreatment with a hyperosmolar urea solution did not change ACE activity or cause release of ACE from the microvessels, although lactic dehydrogenase and lysosomal enzymes were released. Pretreatment with captopril caused a lag in the subsequent degradation of Hip-His-Leu, presumably reflecting dissociation of inhibitor from the cell-associated enzyme. ACE activity was unaffected by hypoxic or anoxic incubation conditions. The ability to measure ACE activity of the microvessels in vitro provides a unique opportunity to study the properties of the enzyme in intact cerebrovascular endothelial cells.

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Section: Figure 6 Angiotensin-converting Enzyme Activity In Intact MImentioning

confidence: 64%

Properties of angiotensin-converting enzyme in intact cerebral microvessels.

Brecher¹,

Tercyak²,

Chobanian³

1981

Hypertension

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“…Although brain uptake of tritiated water has been thought to be only flow limited, recent work by Raichle et al 13 suggests that water uptake is partly diffusion or permeability limited in the brain. Now, if BUI were only a function of blood flow in these experiments, one would expect the BUI to be a function of 3 C 3-0-methyl-D-glucose ( M C 3-0-methyl-D-glucose brain/injectate) distribution in the regions with increased blood flow was described by Pardridge and Oldendorf u recently. There is further evidence to support the contention that BUI changes do not simply reflect blood flow changes.…”

Section: Comparison Of*h 2 O Uptake (Ratio Of Injected To Recovered Wmentioning

confidence: 67%

“…1 Previous studies have shown that both hyperosmotic blood-brain barrier injury and ischemia cause an increase in facilitated transfer of glucose analogues from blood to brain. 2 ' 3 The objective of this investigation was to evaluate the effect of altered oxygen saturation and carbon dioxide tension on the transport rather than metabolism of the glucose in the brain. Therefore, the non-metabolizable 3-0-methyl-D-glucose* and partially metabolizable 2-deoxy-Dglucose, 5 known competitors for the binding side of glucose substrate on the carrier molecule, were chosen for this investigation.…”

Section: Introductionmentioning

confidence: 99%

Effects of Oxygen Saturation and Pco ₂ on Brain Uptake of Glucose Analogues in Rabbits

Berson

Spatz

Klatzo

1975

Stroke

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Abstract:Effects of Oxygen Saturation and Pco, on Brain Uptake of Glucose Analogues in Rabbits• The effect of oxygen saturation and Pco, on brain uptake of glucose analogues was studied in rabbits. Using a modified Oldendorf technique, l4 C-labeled glucose analogues with a 3 H 2 O reference standard were introduced into the cerebral circulation via the common carotid artery, and the radioactivity of the ipsilateral cerebral cortex was counted and expressed in terms of a brain uptake index (BUI).Severe hypoxia (oxygen saturation < 18%) resulted in approximately a 40% decrease in the BUI of 2-deoxy-D-glucose and a 45% decrease in the BUI of 3-0-methyl-D-glucose. Severe hypercapnia (Pco, = 100 mm Hg) caused a 45% decrease in the BUI of both of these glucose analogues. Hypercapnia superimposed on severe hypoxia had no additional effect. Hypocapnia (Pco, = 15 mm Hg) increased the BUI of 3-0-methyl-D-glucose by 35% of the control value, and this increase was extremely sensitive to competitive inhibition. When BUI values were plotted against pH rather than Pco, for the same experiments, there was a good correlation with the calculated linear regression.These results are compared with previous findings on pathologically induced changes in brain uptake of glucose analogues, and the possible role of blood flow is considered in detail. Additional Key Wordshypoxia hypercapnia hypocapnia hyperoxia glucose analogue transport across blood-brain barrier

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“…The elevated brain to plasma glucose concentration ratio supports this speculation (Mayman et al, 1964). It is known that hyperosmolar solutions have an effect on the permeability of the blood-brain barrier (Broman and Lindberg-Broman, 1945;Rapoport et al, 1971) and both Spatz et al (1972) and Pollay (1975) have presented evidence for increased transport of glucose or glucose analogs into brain following infusion of hyperosmolar urea into cerebral arteries (carotid and vertebral, respectively). The fact that entry of glycerol itself into brain was not enhanced after administration of hyperosmolar glycerol does not necessarily rule out this mechanism as an explanation for the increase in brain glucose.…”

Section: Glycerol and Brain Metabolismmentioning

confidence: 99%

“…Glycerol is a gluconeogenic precursor in liver (Burch et al, 1970;Woods and Krebs, 1973) and glucose is the major source of metabolic fuel for brain; therefore, this is an important consideration. Furthermore, hyperosmolar solutions per se appear to enhance the amount of glucose removed from the blood by the brain (Spatz et al, 1972;Pollay, 1975). Penetration of glycerol into brain with reversal of the osmotic gradient between blood and brain and secondarily increased intracranial pressure (''rebound") may also be a clinical problem (Waterhouse and Coxon, 1970;Troupp et al, 1971;Guisado et al, 1974;Guisado et al, 1975;Rottenberg et al, 1977).…”

mentioning

confidence: 99%

Effects of a Single Therapeutic Dose of Glycerol on Cerebral Metabolism in the Brains of Young Mice: Possible Increase in Brain Glucose Transport and Glucose Utilization

Thurston

Hauhart

Dirgo

1981

Journal of Neurochemistry

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This is a study of the effects of a single “therapeutic” dose of glycerol [2 g(22 mmol)/kg i.p.] on brain carbohydrate and energy metabolism in normal nursing weanling mice. Findings were correlated with brain water and electrolyte content and with metabolite changes in plasma, red blood cells, and liver. Plasma glycerol levels peaked at 21 mM 7.5 min after injection and returned to the control value, 0.16 mM, by 2 h. Plasma Na+ concentration decreased and plasma protein increased for as long as 2 h after injection. Although red blood cells were freely permeable to glycerol, there was no evidence for glycerol metabolism in these cells. Glycerol levels in liver paralleled those in plasma. Glycerol injection increased liver glucose concentration 23% and doubled hepatic glycerol‐1‐phosphate levels. Liver ATP levels were reduced 24% after glycerol injection. Brain water concentration was significantly reduced from 7.5 min to 30 min after glycerol injection; brain Na+ and K+ levels were unchanged. There was no evidence for glycerol entry into brain (the amount detected in brain tissue could be explained by the glycerol content in the blood of the brain). While plasma glucose increased 33%, brain glucose increased 87%. Concomitantly there were statistically significant increases in fructose‐1,6‐diphosphate, lactate, α‐ketoglutarate, and malate levels. The disproportionately high brain glucose value suggests increased transport of glucose from the blood to the brain. Increases in fructose‐1,6‐diphosphate, lactate, α‐ketoglutarate, and malate are compatible with an increased metabolic flux in the glycolytic pathway and Krebs citric acid cycle. As has been previously shown for urea and/or mannitol, these changes may result from the effects of the hyperosmolar glycerol solution on the blood‐brain barrier and on cerebral glucose utilization. The sustained lowering of plasma Na+ concentration after a single “therapeutic” glycerol injection suggests a need for monitoring plasma Na+ levels in the clinical situation. Possible lowering of hepatic ATP levels by the use of glycerol in humans is another concern.

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The Effects of Hypertonic Urea on the Blood-Brain Barrier and on the Glucose Transport in the Brain

Cited by 15 publications

References 17 publications

Properties of angiotensin-converting enzyme in intact cerebral microvessels.

Properties of angiotensin-converting enzyme in intact cerebral microvessels.

Effects of Oxygen Saturation and Pco ₂ on Brain Uptake of Glucose Analogues in Rabbits

Effects of a Single Therapeutic Dose of Glycerol on Cerebral Metabolism in the Brains of Young Mice: Possible Increase in Brain Glucose Transport and Glucose Utilization

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The Effects of Hypertonic Urea on the Blood-Brain Barrier and on the Glucose Transport in the Brain

Cited by 15 publications

References 17 publications

Properties of angiotensin-converting enzyme in intact cerebral microvessels.

Properties of angiotensin-converting enzyme in intact cerebral microvessels.

Effects of Oxygen Saturation and Pco 2 on Brain Uptake of Glucose Analogues in Rabbits

Effects of a Single Therapeutic Dose of Glycerol on Cerebral Metabolism in the Brains of Young Mice: Possible Increase in Brain Glucose Transport and Glucose Utilization

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Effects of Oxygen Saturation and Pco ₂ on Brain Uptake of Glucose Analogues in Rabbits