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.

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.

Role of nitric oxide in the regulation of glucose kinetics in response to endotoxin in dogs

2001 ◽  
Vol 91 (1) ◽  
pp. 130-136 ◽  
Author(s):  
H. S. Moeniralam ◽  
F. Sprangers ◽  
E. Endert ◽  
M. T. Ackermans ◽  
J. J. B. Van Lanschot ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
E Coli ◽  
Glucose Levels ◽  
High Doses ◽  
Glucose Plasma

The purpose of the present in vivo study was to determine the role of nitric oxide (NO) in the regulation of glucose metabolism in response to endotoxin by blocking NO synthesis with NG-monomethyl-l-arginine (l-NMMA). In five dogs, the appearance and disappearance rates of glucose (by infusion of [6,6-2H2]glucose), plasma glucose concentration, and plasma hormone concentrations were measured on five different occasions: saline infusion, endotoxin alone ( E coli, 1.0 μg/kg iv), and endotoxin administration plus three different doses of primed, continuous infusion of l-NMMA. Endotoxin increased rate of appearance of glucose from 13.7 ± 1.6 to 23.6 ± 3.3 μmol · kg−1· min−1( P < 0.05), rate of disappearance of glucose from 13.9 ± 1.1 to 24.8 ± 3.1 μmol · kg−1· min−1( P < 0.001), plasma lactate from 0.5 ± 0.1 to 1.7 ± 0.1 mmol/l ( P < 0.01), and counterregulatory hormone concentrations. l-NMMA did not affect the rise in rate of appearance and disappearance of glucose, plasma lactate, or the counterregulatory hormone response to endoxin. Plasma glucose levels were not affected by endotoxin with or withoutl-NMMA. In conclusion, in vivo inhibition of NO synthesis by high doses of l-NMMA does not affect glucose metabolism in response to endotoxin, indicating that NO is not a major mediator of glucose metabolism during endotoxemia in dogs.

scholarly journals Inhibition of Neuronal Nitric Oxide Synthase by 7-Nitroindazole: Effects upon Local Cerebral Blood Flow and Glucose Use in the Rat

1995 ◽  
Vol 15 (5) ◽  
pp. 766-773 ◽  
Author(s):  
Paul A. T. Kelly ◽  
Isobel M. Ritchie ◽  
Gordon W. Arbuthnott
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Physiological Role ◽  
Neuronal Nitric Oxide Synthase ◽  
Conscious Rat ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
The Brain

The novel nitric oxide synthase inhibitor 7-nitroindazole (7-NI) is relatively specific for the neuronal isoform of the enzyme and in this study we have used this compound to investigate the physiological role of perivascular nitric oxide-containing nerves in the cerebrovascular bed. Following injection of 7-NI (25 or 50 mg/kg, i.p.), cerebral blood flow and glucose utilization were measured in the conscious rat using the fully quantitative [14C]iodoantipyrine and 2-[14C]deoxyglucose techniques, respectively. Neither dose of the drug produced any change in arterial blood pressure, confirming a lack of effect upon the endothelial isoform of the enzyme, although there was a pronounced decrease in heart rate (−28% by 10 min postinjection). Throughout the brain 25 mg/kg 7-NI i.p. resulted in decreases in blood flow of between −20% in the hippocampus and −58% in the substantia nigra. Increasing the dose to 50 mg/kg resulted in a further generalized decrease, to almost −60% in parts of the thalamus and hippocampus, but in every animal this higher dose of 7-NI also produced randomly distributed areas of relative hyperaemia, which were most commonly found in those areas where the most intense hypoperfusion was otherwise in evidence. Despite these changes in blood flow, in all but a very few areas of the brain no significant decrease in glucose use was measured at either of the two doses of 7-NI. Thus despite the greater specificity of 7-NI for neuronal nitric oxide synthase, the cerebrovascular effects of the drug in vivo are very similar to that reported for the arginine analogues. However, these data do suggest that nitric oxide-releasing neurones in the brain may have an important role to play in the regulation of cerebral blood flow.

Cortical NOS inhibition raises the lower limit of cerebral blood flow-arterial pressure autoregulation

1999 ◽  
Vol 276 (4) ◽  
pp. H1253-H1262 ◽  
Author(s):  
Stephen C. Jones ◽  
Carol R. Radinsky ◽  
Anthony J. Furlan ◽  
Douglas Chyatte ◽  
Alejandro D. Perez-Trepichio
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Pressure ◽  
Arterial Blood Pressure ◽  
Lower Limit ◽  
Blood Withdrawal ◽  
Arterial Blood ◽  
Pressure Autoregulation

The maintenance of constant cerebral blood flow (CBF) as arterial blood pressure is reduced, commonly referred to as CBF-pressure autoregulation, is typically characterized by a plateau until the vasodilatory capacity is exhausted at the lower limit, after which flow falls linearly with pressure. We investigated the effect of cortical, as opposed to systemic, nitric oxide synthase (NOS) inhibition on the lower limit of CBF-pressure autoregulation. Forty-four Sprague-Dawley rats were anesthetized with halothane and N2O in O2. With a closed cranial window placed the previous day in a ventilated and physiologically stable preparation, we determined the CBF using laser-Doppler flowmetry. Animals with low reactivity to inhaled CO2 and suffused ADP or ACh were excluded. Five arterial pressures from 100 to 40 mmHg were obtained with controlled hemorrhagic hypotension under cortical suffusion with artificial cerebrospinal fluid (aCSF) and then again after suffusion for 35 ( n = 5) and 105 min ( n = 10) with aCSF, 10−3 M N ω-nitro-l-arginine (l-NNA; n = 12), or 10−3 M N ω-nitro-d-arginine (d-NNA; n = 5). An additional group ( n = 7) was studied after a 105-min suffusion of l-NNA followed by a single blood withdrawal procedure. The lower limit of autoregulation was identified visually by four blinded reviewers as a change in the slope of the five-point plot of CBF vs. mean arterial blood pressure. The lower limit of 90 ± 4.3 mmHg after 105 min of 1 mMl-NNA suffusion was increased compared with the value in the time-control group of 75 ± 5.3 mmHg ( P < 0.01; ANOVA) and the initial value of 67 ± 3.7 mmHg ( P < 0.001). The lower limit of 84 ± 5.9 mmHg in seven animals with 105 min of suffusion of 1 mM l-NNA without previous blood withdrawal was significantly increased ( P < 0.01) in comparison with 70 ± 1.9 mmHg from those with just aCSF suffusion ( n = 37). No changes in lower limit for the other agents or conditions, including 105 or 35 min of aCSF or 35 min of l-NNA suffusion, were detected. The lack of effect on the lower limit withd-NNA suffusion suggests an enzymatic mechanism, and the lengthyl-NNA exposure of 105 min, but not 35 min, suggests inhibition of a diffusionally distant NOS source that mediates autoregulation. Thus cortical suffusion ofl-NNA raises the lower limit of autoregulation, strongly suggesting that nitric oxide is at least one of the vasodilators active during hypotension as arterial pressure is reduced from normal.

Effects of striatal nitric oxide production on regional cerebral blood flow and seizure development in rats exposed to extreme hyperoxia

2015 ◽  
Vol 119 (11) ◽  
pp. 1282-1288 ◽  
Author(s):  
Heath G. Gasier ◽  
Ivan T. Demchenko ◽  
Barry W. Allen ◽  
Claude A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Brain Structures ◽  
Nitric Oxide Production ◽  
Regional Cerebral Blood ◽  
Oxide Production ◽  
Arterial Blood ◽  
The Brain

The endogenous vasodilator and signaling molecule nitric oxide has been implicated in cerebral hyperemia, sympathoexcitation, and seizures induced by hyperbaric oxygen (HBO2) at or above 3 atmospheres absolute (ATA). It is unknown whether these events in the onset of central nervous system oxygen toxicity originate within specific brain structures and whether blood flow is diverted to the brain from peripheral organs with high basal flow, such as the kidney. To explore these questions, total and regional cerebral blood flow (CBF) were measured in brain structures of the central autonomic network in anesthetized rats in HBO2at 6 ATA. Electroencephalogram (EEG) recordings, cardiovascular hemodynamics, and renal blood flow (RBF) were also monitored. As expected, mean arterial blood pressure and total and regional CBF increased preceding EEG spikes while RBF was unaltered. Of the brain structures examined, the earliest rise in CBF occurred in the striatum, suggesting increased neuronal activation. Continuous unilateral or bilateral striatal infusion of the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester attenuated CBF responses in that structure, but global EEG discharges persisted and did not differ from controls. Our novel findings indicate that: 1) cerebral hyperemia in extreme HBO2in rats does not occur at the expense of renal perfusion, highlighting the remarkable autoregulatory capability of the kidney, and 2) in spite of a sentinel increase in striatal blood flow, additional brain structure(s) likely govern the pathogenesis of HBO2-induced seizures because EEG discharge latency was unchanged by local blockade of striatal nitric oxide production and concomitant hyperemia.

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.

Intracarotid Infusion of the Nitric Oxide Synthase Inhibitor, l-NMMA, Modestly Decreases Cerebral Blood Flow in Human Subjects

2000 ◽  
Vol 93 (3) ◽  
pp. 699-707 ◽  
Author(s):  
Shailendra Joshi ◽  
William L. Young ◽  
D. Hoang Duong ◽  
Noeleen D. Ostapkovich ◽  
Beverly D. Aagaard ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vascular Reactivity ◽  
Human Subjects ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arginine Infusion ◽  
Blood Concentrations ◽  
Arterial Blood ◽  
Induced Hypertension

Background The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-L-arginine (L-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid L-arginine would reverse its effect. Methods In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid L-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during L-NMMA infusion, and after L-NMMA during L-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of L-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of L-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5). Results Infusion of L-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg; P &lt; 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml. 100 g-1. min-1; P &lt; 0.005) for 10 min. Intracarotid l-arginine infusion after L-NMMA (protocol 3) reversed the effect of L-NMMA. Bolus L-NMMA (protocol 4) increased MAP by 20% (80 +/- 11 to 96+/-13 mmHg; P&lt; 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml. 100 g-1. min-1; P&lt; 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9 to 95 +/- 6 mmHg; P = 0.001) but did not affect CBF. Conclusions The results suggest that intracarotid L-NMMA modestly decreases CBF, and the background tone of cerebral resistance vessels may be relatively insensitive to NOS inhibition by the intraarterial route.

scholarly journals Cerebral Blood Flow, Brain pH, and Oxidative Metabolism in the Cat during Severe Insulin-Induced Hypoglycemia

1982 ◽  
Vol 2 (3) ◽  
pp. 337-346 ◽  
Author(s):  
John M. Cilluffo ◽  
Robert E. Anderson ◽  
John D. Michenfelder ◽  
Thoralf M. Sundt
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Severe Hypoglycemia ◽  
Energy Reserves ◽  
Cerebral Tissue ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Eeg Abnormalities ◽  
Brain Ph ◽  
Eeg Changes

The effects of severe hypoglycemia on brain pH, cerebral blood flow (CBF), and other physiologic and metabolic parameters were studied in 26 cats subjected to insulin hypoglycemia. Two groups were utilized to compare the effects of anesthesia. The halothane group was composed of 14 animals and the barbiturate group contained 12 animals. Insulin was administered by both the intravenous and intramuscular routes until there was a severe electroencephalographic (EEG) change or until 6 h had elapsed. The cerebral responses to hypoglycemia demonstrated the following: CBF was unaffected by severe hypoglycemia in normotensive animals with or without EEG changes; brain pH was essentially constant in all groups regardless of glucose levels, CBF, or EEG; and the EEG abnormalities corresponded closely to brain glucose levels. Cerebral adenosine triphosphate and phosphocreatine levels were lowest in the animals with isoelectric EEGs. We conclude that CBF and brain pH in the normotensive cat under general anesthesia are relatively unaffected by insulin hypoglycemia despite the presence of severe EEG changes and cerebral energy reserves. The study suggests that the Paco2–CBF response curve is not dependent upon the metabolic integrity of cerebral tissue and is mediated by pathways separate from those of autoregulation.

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.

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