Effects of elevated plasma epinephrine on glucose utilization and blood flow in conscious rat brain

1997 ◽  
Vol 272 (4) ◽  
pp. H1666-H1671
Author(s):  
N. Horinaka ◽  
N. Artz ◽  
M. Cook ◽  
C. Holmes ◽  
D. S. Goldstein ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Utilization ◽  
Brain Structures ◽  
Plasma Epinephrine ◽  
Conscious Rat ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma ◽  
Student’S T ◽  
Normal Controls

Acute glucoprivation increases cerebral blood flow (CBF), which is often attributed to the associated rise in plasma epinephrine levels. This study examined directly the effects of comparable increases in plasma epinephrine levels achieved by continuous intravenous infusions of epinephrine in normoglycemic, unanesthetized rats on local and overall CBF and cerebral glucose utilization (1CMRglc). CBF was determined by the autoradiographic [14C]iodoantipyrine method in six unanesthetized rats in which epinephrine dissolved in 1% ascorbic acid-1 mM EDTA was infused at a rate of 1 microg/min and in five normal controls infused with the vehicle alone. 1CMRglc was determined by the autoradiographic [14C]deoxyglucose method in six conscious rats infused similarly with the epinephrine solution and in six normal controls treated with the vehicle alone. The epinephrine infusions raised arterial plasma epinephrine levels 10- to 20-fold and increased arterial blood pressure and plasma glucose levels. Local CBF, however, was significantly changed (P < 0.05, Student's t-test) in only 2 of 25 structures examined, and the changes were decreases not increases. 1CMRglc was not changed significantly in any of 42 brain structures examined, and average blood flow and glucose utilization in the brain as a whole were unaffected. These results show that high circulating levels of epinephrine similar to those accompanying glucoprivation alter neither local nor overall CBF and glucose utilization and cannot explain the increases in CBF associated with glucoprivation.

scholarly journals Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

1997 ◽  
Vol 17 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Naoaki Horinaka ◽  
Nicole Artz ◽  
Jane Jehle ◽  
Shinichi Takahashi ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

Local cerebral blood flow and glucose utilization after blood exchange with a hemoglobin-based O2 carrier in conscious rats

1993 ◽  
Vol 265 (4) ◽  
pp. H1243-H1248 ◽  
Author(s):  
K. Waschke ◽  
H. Schrock ◽  
D. M. Albrecht ◽  
K. van Ackern ◽  
W. Kuschinsky
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Utilization ◽  
Brain Structures ◽  
Control Group ◽  
Local Cerebral Blood Flow ◽  
Conscious Rats ◽  
Cerebral Glucose Utilization ◽  
Arterial Blood ◽  
Blood Exchange

The effects of a blood exchange on cerebral blood flow and glucose utilization were studied. A near to total blood exchange (hematocrit < 3%) was achieved in conscious rats by isovolemic hemodilution. Ultrapurified, polymerized, bovine hemoglobin (UPBHB) served as a blood substitute. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 34 brain structures of conscious rats by means of the ido[14C]antipyrine and the 2-[14C]-deoxy-D-glucose methods. A group of rats without blood exchange served as control. After blood exchange LCBF increased from 36 to 126% in the different brain structures resulting in a nearly doubled mean cerebral blood flow (+82%). LCGU increased only moderately by 0-24%. Significant increases in LCGU were observed in 16 brain structures. Mean cerebral glucose utilization slightly increased (+14%). The relationship between LCGU and LCBF was found to be tight both in the control group (r = 0.95) as well as after blood replacement (r = 0.94), although it was reset to a higher overall LCBF-to-LCGU ratio. The profound increases in LCBF observed after blood exchange, which were not paralleled by comparable increases in LCGU, might be explained by a reduction of blood viscosity after blood exchange. Additional effects of blood exchange observed in the present study were an increase of mean arterial blood pressure and a decline of heart rate. The results indicate that replacement of blood with the hemoglobin-based oxygen carrier UPBHB appears to meet the cerebral circulatory and metabolic demands of the brain tissue.

Unaltered cerebral blood flow during hypoglycemic activation of the sympathochromaffin system in humans

1993 ◽  
Vol 265 (4) ◽  
pp. R883-R887 ◽  
Author(s):  
W. J. Powers ◽  
P. J. Boyle ◽  
I. B. Hirsch ◽  
P. E. Cryer
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Plasma Glucose ◽  
Plasma Norepinephrine ◽  
Plasma Catecholamine ◽  
Primary Role ◽  
Plasma Epinephrine ◽  
Glucose Levels ◽  
Positron Emission ◽  
Arterial Plasma

To determine if increases in plasma epinephrine and norepinephrine caused by hypoglycemia are associated with increments in cerebral blood flow (CBF), we measured CBF with positron emission tomography in normal humans at ambient fasting arterial plasma glucose levels and at clamped plasma glucose levels of 5.3, 3.5, and 2.8 mmol/l using the hyperinsulinemic, stepped hypoglycemic clamp technique. Despite significant increases in plasma epinephrine to 7,340 +/- 350 (SE) pmol/l and in plasma norepinephrine to 3.32 +/- 0.35 nmol/l, mean hemispheric CBF (41 +/- 1, 49 +/- 1, 48 +/- 2, and 51 +/- 3 ml x 100 g-1 x min-1) remained constant at the ambient (5.2), 5.3, 3.5, and 2.8 mmol/l glycemic levels, respectively. Furthermore, there was no correlation between CBF and either plasma epinephrine levels ranging from 160 to 10,580 pmol/l or plasma norepinephrine levels ranging from 0.56 to 5.10 nmol/l. Failure to demonstrate any dose-response relationship between plasma catecholamine levels and CBF argues against their primary role in cerebrovascular control during hypoglycemia.

Increased Cerebral Blood Flow and Plasma Epinephrine in Hypoglycemic, Preterm Neonates

PEDIATRICS ◽  
1990 ◽  
Vol 85 (2) ◽  
pp. 172-176 ◽  
Author(s):  
O. Pryds ◽  
N. J. Christensen ◽  
B. Friis-Hansen
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Glucose ◽  
Preterm Neonates ◽  
Plasma Norepinephrine ◽  
Plasma Epinephrine ◽  
Intravenous Glucose ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Blood Glucose Levels

Cerebral blood flow, plasma epinephrine, and plasma norepinephrine were measured in 25 spontaneously breathing, preterm neonates (mean gestational age 30.4 weeks) 2 hours after birth, during a routine screening for low blood glucose levels. Increased cerebral blood flow and plasma epinephrine values were observed when blood glucose levels were low, whereas plasma norepinephrine was constant throughout the blood glucose range. Hypoglycemia (defined as blood glucose concentration &lt;30 mg/dL) was found in 13 neonates who were treated with intravenous glucose and milk enterally. Blood glucose levels were normal in the remaining 12 control neonates who received milk by a gastric line. Approximately 30 minutes after treatment with intravenous glucose and/or milk, cerebral blood flow had decreased by a mean of 11.3% in the 13 hypoglycemic neonates but was still 37.5% higher than cerebral blood flow in the control neonates despite normalization of plasma epinephrine concentration. Mean arterial blood pressure and blood gas values were identical between groups throughout the investigation. It is suggested that a normal coupling between cerebral metabolic demands and flow is present in very preterm neonates and that epinephrine may play a role in the cerebral hyperperfusion. Although none of the neonates had clinical signs of hypoglycemia, the data suggest that counterregulatory mechanisms are invoked when blood glucose values are &lt;30 to 45 mg/dL.

Interdependency of local capillary density, blood flow, and metabolism in rat brains

1986 ◽  
Vol 251 (6) ◽  
pp. H1333-H1340 ◽  
Author(s):  
B. Klein ◽  
W. Kuschinsky ◽  
H. Schrock ◽  
F. Vetterlein
Keyword(s):  
Blood Flow ◽  
Glucose Utilization ◽  
Gamma Globulin ◽  
Fluorescein Isothiocyanate ◽  
Brain Structures ◽  
Capillary Density ◽  
Brain Capillaries ◽  
Local Cerebral Blood Flow ◽  
High Degree ◽  
The Relationship

Previous investigations have established a strong correlation between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). In the present study the relationship between density of perfused brain capillaries and LCBF or LCGU was investigated in conscious and anesthetized rats. Perfused capillaries were stained by labeling the plasma with the gamma globulin-coupled fluorochromes, fluorescein isothiocyanate (FITC) and lissamine-rhodamine B 200 (RB 200). The density of perfused capillaries was determined in 12 different brain structures by fluorescence microscopy of embedded brain sections following coronal sectioning in a cryostat. Significant differences were found among brain structures investigated; the lowest density of perfused capillaries was found in the white matter (e.g., corpus callosum 162 fragments/mm2), whereas the highest values were determined in the structures of the auditory system (e.g., inferior colliculus 810 fragments/mm2). LCBF and LCGU were measured in two separate groups of rats using standard autoradiographic methods. In all three experimental groups, the same structures were identified and measured with a high degree of accuracy and local resolution. Density of perfused capillaries correlated well with LCBF (r = 0.93) and even better with LCGU (r = 0.97). In addition to the relationship between LCGU and LCBF established by earlier studies, these data show the intimate interrelationship between LCGU, density of perfused capillaries, and LCBF.

Capsaicin-sensitive nerves are required for glucostasis but not for catecholamine output during hypoglycemia in rats

1990 ◽  
Vol 258 (1) ◽  
pp. E212-E219 ◽  
Author(s):  
X. F. Zhou ◽  
K. H. Jhamandas ◽  
B. G. Livett
Keyword(s):  
Blood Glucose ◽  
Somatostatin Analogue ◽  
Plasma Epinephrine ◽  
Conscious Rat ◽  
Glucose Response ◽  
Conscious Rats ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sensory Fibers

We have studied the glucose response and catecholamine (CA) response to insulin in the conscious rat to evaluate the role of sensory fibers in these responses in animals pretreated with capsaicin as neonates. In contrast to previous results obtained in anesthetized rats (Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 370: 201-215, 1986; Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 391: 511-526, 1987.), in conscious rats, insulin (1 IU/kg iv) produced only a mild hypoglycemia, which quickly returned to resting levels and caused no significant changes in plasma epinephrine levels. Somatostatin and SMS-(201-995), a somatostatin analogue, both potentiated and prolonged the insulin-induced hypoglycemia, resulting in an increase in circulating CA levels that was suppressed by hexamethonium and atropine. In capsaicin-pretreated rats the blood glucose levels at 90 min after insulin were significantly lower than those in vehicle-pretreated rats both in the presence (1 IU/kg insulin, 48 +/- 6 vs. 92 +/- 6 mg/100 ml, P less than 0.01) and absence (10 IU/kg insulin, 38 +/- 4 vs. 51 +/- 2 mg/100 ml, P less than 0.01) of SMS-(201-995). The CA levels in capsaicin-pretreated rats at 90 min after insulin were higher than in vehicle-pretreated rats (epinephrine levels: 27 +/- 4 vs. 10 +/- 1 pmol/ml in 1 IU/kg insulin, P less than 0.01; 64 +/- 14 vs. 25 +/- 5 pmol/ml in 10 IU/kg insulin, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Perivascular Microapplication of Endothelin-1: A New Model of Focal Cerebral Ischaemia in the Rat

1993 ◽  
Vol 13 (5) ◽  
pp. 865-871 ◽  
Author(s):  
John Sharkey
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischaemia ◽  
Dorsal Hippocampus ◽  
Focal Cerebral Ischaemia ◽  
Local Cerebral Blood Flow ◽  
Guide Cannula ◽  
Conscious Rat ◽  
Endothelin 1 ◽  
Arterial Blood

In the present study, we describe the effects of perivascular microapplication of the potent vasoconstrictor peptide endothelin-1 (Et-1; (120 pmol in 3 μl), delivered via a guide cannula stereotaxically positioned above the left cerebral artery (MCA) of the conscious male Sprague–Dawley rat. Ten minutes after the administration of Et-1, mean arterial blood pressure had increased by 20% and profound reductions in local cerebral blood flow (up to 93%) were observed within those brain areas supplied by the MCA. In addition, significant increases in local cerebral blood flow were observed within the globus pallidus (100%), substantia nigra pars reticulata (48%), ventrolateral thalamus (65%), and dorsal hippocampus (74%) ipsilateral to the insult. Twenty-four hours following the insult, the pattern of ischaemic damage was similar to that reported previously following permanent occlusion of the rat MCA. It is suggested that perivascular microapplication of Et-1 may provide a useful model for the study of the functional disturbances associated with focal cerebral ischaemia in the conscious rat.

scholarly journals Brain Glucose Levels in Portacaval-Shunted Rats with Chronic, Moderate Hyperammonemia: Implications for Determination of Local Cerebral Glucose Utilization

1994 ◽  
Vol 14 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Nancy F. Cruz ◽  
Gerald A. Dienel
Keyword(s):  
Glucose Utilization ◽  
Normal Values ◽  
Brain Structures ◽  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Dg Method ◽  
The Brain

Rates of glucose utilization (lCMRglc) in many structures of the brain of fed, portacaval-shunted rats, when assayed with the [14C]deoxyglucose (DG) method in our laboratory, were previously found to be unchanged (30 of 36 structures) or depressed (6 structures) during the first 4 weeks after shunting, but to rise progressively to higher than normal values in 25 of 36 structures from 4–12 weeks. In contrast, lCMRglc, when assayed with the [14C]glucose method in another laboratory, was depressed in most structures of brains of 4–8-week shunted rats that had relatively high brain ammonia levels. There was a possibility that the increases in lCMRglc obtained with the [14C]DG method may have been artifactual, due, in part, to a change in brain glucose content which could alter the value of the lumped constant of the DG method. Brain glucose levels of shunted rats were, therefore, assayed by both direct chemical measurement in freeze-blown samples and by determination of steady-state brain:plasma distribution ratios for [14C]methylglucose; the methylglucose distribution ratio varies as a function of plasma and tissue glucose contents. Within a week after shunting, ammonia levels in blood and brain rose to 0.25–0.30 m M and 0.35–0.70 μmol/g, respectively, and mean plasma glucose levels fell from 9–10 m M to 7.4–8.5 m M, and then remained nearly constant. Brains of fedshunted rats had normal glycogen levels and stable but moderately reduced glucose contents between 1 and 12 weeks (i.e., 1.9–2.2 μmol/g). [14C]Methylglucose distribution ratios were essentially the same as those in controls in 22 brain structures at 2 and 8 weeks after shunting. Because brain glucose levels remained stable from 1 to 12 weeks after shunting, there is no evidence to support the hypothesis that the value of the lumped constant would have changed and caused an artifactual rise in lCMRglc.

Metabolic Effect and Uptake of [3H]Digoxin in the Forearm of Man

1972 ◽  
Vol 42 (5) ◽  
pp. 567-577
Author(s):  
R. I. Ogilvie ◽  
G. A. Klassen
Keyword(s):  
Blood Flow ◽  
Oleic Acid ◽  
Forearm Blood Flow ◽  
Digoxin Concentration ◽  
Normal Male ◽  
Ethanol Group ◽  
Arterial Blood ◽  
Electrolyte Flux ◽  
Arterial Plasma

1. The forearm perfusion technique was used to study the effect of intra-arterial injections of ethanol with or without digoxin on the metabolism and electrolyte flux of forearm tissues in normal male volunteers. 2. In six subjects infusion of ethanol alone (2·9 mg/min over 30 min) resulted in no alterations of forearm blood flow, O2 consumption, carbohydrate metabolism, or flux of potassium and calcium. Although there was no change in extraction of [14C]oleic acid, a significant net output of oleic and total free fatty acids was observed from both deep venous and superficial venous systems. 3. In six subjects the intra-arterial infusion of [3H]digoxin (0·09 μg/min with ethanol, 2·9 mg/min over 30 min) resulted in no alteration of forearm blood flow. During the steady state achieved after 5–8 min of perfusion, 50·3% of the calculated local arterial plasma digoxin concentration of 2·73 μg/l was extracted by the deep venous system with a significant increase in glucose extraction. The respiratory quotient and fractional utilization of O2 by glucose increased. No change in extraction of [14C]oleic acid from arterial blood was observed. However, the net output of oleic and total free acids from both deep and superficial venous systems was insignificant in comparison with that observed in the ethanol control subjects. The changes in K+ flux were similar to those noted in the ethanol group. In the post-digoxin period there was a significantly increased uptake of Ca2+ by forearm tissues. 4. This is the first demonstration of the stimulatory effects of digoxin on glucose metabolism, the antilipolytic effects of this drug and its effect on Ca2+ fluxes in vivo in man.

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