Abstract
The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1309-1318 |
| Number of pages | 10 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 17 |
| Issue number | 12 |
| State | Published - Dec 1997 |
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Keywords
- [C]Iodoantipyrine
- Adenosine receptors
- ATP-sensitive K channels
ASJC Scopus subject areas
- Endocrinology
- Neuroscience(all)
- Endocrinology, Diabetes and Metabolism
Cite this
Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. / Horinaka, Naoaki; Kuang, Tang Yong; Pak, Hazel; Wang, Robert; Jehle, Jane; Kennedy, Charles; Sokoloff, Louis.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 17, No. 12, 12.1997, p. 1309-1318.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats
AU - Horinaka, Naoaki
AU - Kuang, Tang Yong
AU - Pak, Hazel
AU - Wang, Robert
AU - Jehle, Jane
AU - Kennedy, Charles
AU - Sokoloff, Louis
PY - 1997/12
Y1 - 1997/12
N2 - The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.
AB - The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.
KW - [C]Iodoantipyrine
KW - Adenosine receptors
KW - ATP-sensitive K channels
UR - http://www.scopus.com/inward/record.url?scp=0030694276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030694276&partnerID=8YFLogxK
M3 - Article
C2 - 9397030
AN - SCOPUS:0030694276
VL - 17
SP - 1309
EP - 1318
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 12
ER -