Roles of neuronal nitric oxide synthase, oxidative stress, and propofol in N-methyl-D-aspartate-induced dilatation of cerebral arterioles

Abstract

Background: It remains unclear whether N-methyl-d-aspartate (NMDA) receptors contribute to cerebral parenchymal vasodilatation, and any effects of clinically used anaesthetics on the dilatation. The present study was designed to examine whether NMDA induces neuronal nitric oxide synthase (NOS)-mediated dilatation, in the cerebral parenchymal arterioles, and whether propofol and superoxide modulate the dilatation in relation to the NMDA receptor activation. Methods: The cerebral parenchymal arterioles within rat brain slices were monitored by a computer-assisted microscopy, and the vasodilatation in response to NMDA (10-7 to 10-5 M) was evaluated. Immunofluorescence analysis to neuronal and endothelial NOS and measurement of levels of superoxide and nitric oxide within the arteriole were simultaneously performed.ResultsPropofol, an NMDA receptor antagonist MK801, and a neuronal NOS antagonist S-methyl-l-thiocitrulline (SMTC) reduced NMDA-induced dilation, whereas a superoxide inhibitor, Tiron, and NADPH oxidase inhibitor, gp91ds-tat, augmented NMDA-induced dilatation. Immunofluorescence analysis revealed distribution of neuronal NOS in both endothelial and smooth muscle cells in addition to neuronal cells. NMDA-induced superoxide and nitric oxide within the parenchymal arterioles. The increased superoxide within the arteriole was similarly inhibited by MK801, SMTC, gp91ds-tat, propofol, and a neuronal NOS antagonist vinyl-L-NIO, whereas the level of nitric oxide was reduced by MK801, SMTC, propofol, and vinyl-L-NIO, and it was augmented by gp91ds-tat. Conclusions: NMDA dilates cerebral parenchymal arterioles possibly via neuronal NOS activation, whereas it produces superoxide via NADPH oxidase. In these arterioles, propofol reduces both the dilatation and superoxide production in response to NMDA.© 2011 The Author Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.