N??-Nitro-L-Arginine Methyl Ester Prevents Cerebral Hyperemia by Inhaled Anesthetics in Dogs

Abstract
The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg Nω-nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 ± 4 to 56 ± 6 mL·min−1· 100 g−1 and 43 ± 6 to 78 ± 12 mL·min−1·100 g−1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 ± 0.2; isoflurane, 2.0 ± 0.2 mL·min-1·100 g−1). On the contrary, nitrous oxide increased CBF similarly (40 ±6 to 57 ± 8 mL·min−1·100 g−1), but increased cerebral oxygen consumption (2.2 ± 0.3 to 3.0 ± 0.3 mL·min−1· 100 g−1). L-NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF. These data demonstrate that blockade of NO synthase by L-NAME prevents increased CBF by nitrous oxide, isoflurane, and halothane and suggests that the mechanism of increased CBF with all three anesthetics is mediated via a NO or nitrosothiol mechanism.