Background and Purpose - Hypoxia and hemodilution both reduce arterial oxygen content (CaO2) and increase cerebral blood flow (CBF), but the mechanisms by which hemodilution increases CBF are largely unknown. ATP- sensitive potassium (K(ATP)) channels are activated by intravascular hypoxia, and contribute to hypoxia-mediated cerebrovasodilatation. Although CaO2 can be reduced to equal levels by hypoxia or hemodilution, intravascular PO2 is reduced only during hypoxia. We therefore tested the hypothesis that K(ATP) channels would be unlikely to contribute to cerebrovasodilatation during hemodilution. Methods - Glibenclamide (19.8 μg) or vehicle was injected into the cisterna magna of barbiturate-anesthetized rats. The dose of glibenclamide was chosen to yield an estimated CSF concentration of 10-4 M. Thirty minutes later, some animals underwent either progressive isovolumic hemodilution or hypoxia (over 30 minutes) to achieve a CaO2 of ≃7.5 mL O2/dL. Other animals did not undergo hypoxia or hemodilution and served as controls. Six groups of animals were studied: control/vehicle (n=4), control/glibenclamide (n=4), hemodilution/vehicle (n=10), hemodilution/glibenclamide (n=10), hypoxia/vehicle (n=10), and hypoxia/glibenclamide (n=10). CBF was then measured with 3H-nicotine in the forebrain, cerebellum, and brain stem. Results - In control/vehicle rats, CBF ranged from 72 mL · 100 g-1 · min-1 in forebrain to 88 mL · 100 g-1 · min-1 in the brain stem. Glibenclamide treatment of control animals did not influence CBF in any brain area. Hemodilution increased CBF in all brain areas, with flows ranging from 128 mL · 100 g-1 · min-1 in forebrain to 169 mL · 100 g-1 · min-1 in the brain stem. Glibenclamide treatment of hemodiluted animals did not affect CBF in any brain area. Hypoxia resulted in a greater CBF than did hemodilution, ranging from 172 mL · 100 g-1 · min-1 in forebrain to 259 mL · 100 g-1 · min-1 in the brain stem. Glibenclamide treatment of hypoxic animals significantly reduced CBF in all brain areas (P<0.05). Conclusions - Both hypoxia and hemodilution increased CBF. Glibenclamide treatment significantly attenuated the CBF increase during hypoxia but not after hemodilution. This finding supports our hypothesis that K(ATP) channels do not contribute to increasing CBF during hemodilution. Because intravascular PO2 is normal during hemodilution, this finding supports the hypothesis that intravascular PO2 is an important regulator of cerebral vascular tone and exerts its effect in part by activation of K(ATP) channels in the cerebral circulation.
- Cerebral blood flow
- Potassium channels