Adenosine and cerebrovascular hyperemia during insulin-induced hypoglycemia in newborn piglet

V. J. Ruth, T. S. Park, E. R. Gonzales, J. M. Gidday

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19 Scopus citations

Abstract

The present study tested the hypothesis that adenosine is involved in mediating the hyperemic response of the newborn brain to hypoglycemia. By use of the cranial window and microdialysis-H2 clearance methodologies, changes in the diameter of pial arterioles (25-50 μm), extracellular adenosine concentrations ([ADO]), and local cerebral blood flow (CBF) were examined in isoflurane-anesthetized piglets subjected to insulin-induced hypoglycemia. Blood glucose concentrations ranged from 10 to 18 mg/dl after insulin administration (25 IU/kg/iv). Local CBF in the frontal cortex increased 36 ± 12% (P = 0.014) at 30 min of hypoglycemia (group 1, n = 12; control = 43 ± 3 ml · min-1 · 100 g-1). The mean increase in dialysate [ADO] sampled concurrently from the same cortical area was 59 ± 29% (P = 0.011; control = 0.11 ± 0.02 μM). At 30 min of hypoglycemia, pial diameters increased 55 ± 10% (P = 0.001; group 2, n = 9). The [ADO] in cranial window cerebrospinal fluid (CSF) increased 217 ± 71% (P = 0.04) in response to hypoglycemia (group 3, n = 8; control = 0.016 ± 0.006 μM). Local administration of an adenosine antagonist, 10 μM 8-sulfophenyltheophylline, to the cerebral cortex before hypoglycemia caused a 38% reduction (P = 0.011) in the pial arteriolar response at 30 min of hypoglycemia (group 4, n = 9). Similarly, local superfusion of CSF with 3.7 mM glucose attenuated the hypoglycemia- induced pial dilation 33% (P = 0.039; group 5, n = 9). Perfusion of microdialysis probes with 3.7 mM glucose in the CSF abolished the hypoglycemia-induced increase in dialysate [ADO] (group 1). Pial arteriolar diameters did not change when normoglycemic blood glucose levels were maintained by intravenous glucose after insulin administration (group 6, n = 6). These findings in newborn piglets indicate that hypoglycemia promotes increases in cerebral extracellular [ADO], which contribute to the observed pial dilation and parenchymal hyperemia.

Original languageEnglish
Pages (from-to)H1762-H1768
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume265
Issue number5 34-5
DOIs
StatePublished - 1993

Keywords

  • cerebral blood flow
  • cranial window
  • microdialysis
  • purines

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