Cerebral blood flow during hemodilution and hypoxia in rats - Role of ATP-sensitive potassium channels

Background and Purpose-Hypoxia and hemodilution both reduce arterial oxygen content (Cao,) and increase cerebral blood flow (CBF), but the mechanisms by which hemodilution increases CBF are largely unknown. ATP-sensitive pota ssium (K-ATP) channels are activated by intravascular hypoxia, and contribu te to hypoxia-mediated cerebrovasodilatation. Although CaO2 can be reduced to equal levels by hypoxia or hemodilution, intravascular Po, is reduced on ly during hypoxia. We therefore tested the hypothesis that K-ATP channels w ould be unlikely to contribute to cerebrovasodilatation during hemodilution . Methods-Glibenclamide (19.8 mu g) or vehicle was injected into the cisterna magna of barbiturate-anesthetized rats. The dose of glibenclamide was chos en to yield an estimated CSF concentration of 10(-4) M. Thirty minutes late r, some animals underwent either progressive isovolumic hemodilution or hyp oxia (over 30 minutes) to achieve a CaO2 of approximate to 7.5 mL O-2/dL. O ther animals did not undergo hypoxia or hemodilution and served as controls . Six groups of animals were studied: control/vehicle (n = 4), control/glib enclamide (n = 4), hemodilution/vehicle (n = 10), hemodilution/glibenclamid e (n = 10). hypoxia/vehicle (n = 10), and hypoxia/glibenclamide (n = 10). C BF was then measured with H-3-nicotine in the forebrain, Cerebellum, and br ain 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 trea tment of control animals did not influence CBF in any brain area. Hemodilut ion 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. Gli benclamide treatment of hemodiluted animals did not affect CBF in any brain area. Hypoxia resulted in a greater CBF than did hemodilution, ranging fro m 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 reduce d CBF in all brain areas (P<0.05). Conclusions-Both hypoxia and hemodilution increased CBF. Glibenclamide trea tment significantly attenuated the CBF increase during hypoxia but not afte r hemodilution. This finding supports our hypothesis that K-ATP channels do not contribute to increasing CBF during hemodilution. Because intravascula r PO2 is normal during hemodilution, this finding supports the hypothesis t hat intravascular PO2 is an important regulator of cerebral vascular tone a nd exerts its effect in part by activation of K-ATP channels in the cerebra l circulation.