A cholinergic agonist induces cerebral hyperemia in isoflurane- but not pentobarbital-anesthetized dogs

We tested whether the cerebral blood flow (CBF) response to the cholinergic agonist oxotremorine (OXO) is affected by the choice of anesthetics in dogs. We studied two anesthetics, pentobarbital and isoflurane, which produce similar levels of cerebral metabolic depression but have opposing effects on CBF. We also tested the contribution of nitric oxide (NO, or a NO-containing compound) in mediating the CBF response to OXO by determining whether NO synthase inhibition with N(ω)-nitro-L-arginine methyl ester (L-NAME) would attenuate OXO-induced hyperemia in both anesthetic groups. CBF (microspheres) was measured before and after OXO administration (50 μg · kg^-1 · min^-1 intravenously [IV] for 10 min). Animals were divided randomly to receive OXO alone (n = 10) or L-NAME (40 mg/kg IV) followed by OXO (n = 10). Within each group, half of the animals received pentobarbital anesthesia (30 mg/kg IV) and half received isoflurane (1.4% end-tidal). In pentobarbital-anesthetized animals OXO produced no change in blood flow to cerebrum, caudate, diencephalon, neurohypophysis, or cerebellum in the absence (e.g., cerebrum 37 ± 2 vs 42 ± 5 mL/min/100 g) or presence of L-NAME (e.g., cerebrum, 29 ± 4 vs 30 ± 3 mL · min^-1 · 100 g^-1). In isoflurane-anesthetized animals, however, blood flow to forebrain regions increased after OXO (e.g., cerebrum 108 ± 10 vs 232 ± 15 mL · min^-1 · 100 g^-1; P < 0.05) without alteration in oxygen consumption in cerebrum (CMRO₂) or blood flow to hindbrain regions. In isoflurane-anesthetized animals, L-NAME decreased baseline blood flow to cerebrum, caudate, diencephalon, cerebellum, and neurohypophysis (P < 0.05). L-NAME prevented OXO-induced hyperemia in caudate and diencephalon but not in cerebrum (51 ± 5 vs 81 ± 13 mL · min^-1 · 100 g^-1). We conclude that anesthetics modulate cholinergic-induced cerebral hyperemia. The mechanism for OXO- induced hyperemia is partially due to stimulation of NO synthase and is not associated with an increase in CMRO₂ in cerebrum.