Hypoxia, α₂-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow

We tested the hypothesis that NO synthase inhibition with N(ω)-nitro-L- arginine methyl ester (L-NAME) and α₂-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 ± 4 to 210 ± 30 ml · min^-1 · 100 g^-1 and from 88 ± 7 to 205 ± 27 (±SE) ml · min^-1 · 100 g^-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 ± 15 to 204 ± 38 ml · min^-1 · 100 g^-1. Dex (10 μg/kg iv) reduced normoxic CBF to 54 ± 8 ml · min^-1 · 100 g^-1, and subsequent hypoxia increased CBF to 97 ± 14 ml · min^-1 · 100 g^-1. In a third group pretreated with L-NAME (40 mg/kg iv) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 ± 2 vs. 83 ± 4 ml · min^-1 · 100 g^-1). Hypoxia increased CBF to 177 ± 13 ml · min^-1 · 100 g^-1. Dex after L-NAME further decreased normoxic CBF to 37 ± 3 ml · min^-1 · 100 g^-1, and subsequent hypoxia increased CBF to 106 ± 18 ml · min^-1 · 100 g^-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O₂ transport (CBF x arterial O₂ content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O₂ transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF. These results indicate that 1) CBF responsivity to hypoxia is intact during isoflurane anesthesia despite the relative hyperemia during normoxia, and 2) mediators of hypoxic vasodilation, NO-dependent vasodilation, and α₂- adrenergic vasoconstriction act via additive mechanisms on cerebrovascular tone in the presence of isoflurane anesthesia.