Nitrous oxide increases peripheral blood flow and decreases plasma adrenaline and noradrenaline concentrations in human volunteers: An in vivo nonrandomized clinical and in vitro chromaffin cell culture study

Abstract

Our understanding of the effects of nitrous oxide (N₂O) on the peripheral circulation is incomplete. Therefore, we investigated its effects on peripheral blood flow, skin temperature, and plasma adrenaline (AD) and noradrenaline (NAd) concentrations, which reflect sympathetic nerve activity, in human volunteers and on AD and NAd release from cultured bovine adrenal chromaffin cells. Twenty-three subjects were allocated to three groups based on measurement items. Peripheral blood flow, palm skin temperature, and plasma AD and NAd levels were evaluated using modern laser-Doppler flowmetry, thermography, and high-performance liquid chromatography with a fluorescence detector, respectively. In the in vitro study, cultured bovine adrenal chromaffin cells were used to examine the effects of N₂O on AD and NAd release. The inhalation of N₂O significantly increased peripheral blood flow and palm skin temperature. It also significantly decreased plasma AD and NAd concentrations. The in vitro study revealed that N₂O significantly inhibited acetylcholine (ACh)-induced AD and NAd release from cultured cells, while a high concentration did not affect excess KCl-induced AD and NAd release, suggesting that N₂O interfered with the process between the activation of ACh receptors and opening of voltage-operated Ca²⁺ channels in the plasma membrane. These changes in the peripheral circulation by N₂O were attributed to a decrease in plasma AD and NAd concentrations, which may have been due to the inhibition of sympathetic activity. In addition, the ability of N₂O to reduce plasma AD and NAd concentrations was mediated, at least in part, by the inhibition of their release from the adrenal medulla.