title: Adenosine and cerebrovascular hyperemia during insulin-induced hypoglycemia in newborn piglet.
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 microns), 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 microM). 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 microM). Local administration of an adenosine antagonist, 10 microM 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).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Children's Hospital, University of Helsinki, Finland.
authors.forename: V J
authors.initials: VJ
authors.lastname: Ruth
authors.forename: T S
authors.initials: TS
authors.lastname: Park
authors.forename: E R
authors.initials: ER
authors.lastname: Gonzales
authors.forename: J M
authors.initials: JM
authors.lastname: Gidday
mesh_terms: D000241:Adenosine / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006940:Hyperemia / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*; D007003:Hypoglycemia / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010841:Pia Mater / Q000098:blood supply; D012039:Regional Blood Flow; D013552:Swine; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002245:Carbon Dioxide; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine; D010100:Oxygen