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

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. RESULTS: Propofol, 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.

Does lidocaine provoke clinically significant vasospasm?

Two cases with peripheral vasoconstriction possibly caused by topical application of lidocaine were reported. A potential risk of vasospasm provoked by lidocaine may be a pitfall for anesthesiologists because lidocaine is commonly considered a vasodilator.

Albumin permeability across endothelial cell monolayer exposed to reactive oxygen intermediates: involvement of reversible functional alteration of the cell membrane Ca2+ channels.

This study was designed to test the idea that the redox state of sulfhydryl (SH)-groups in cell-membrane Ca2+ channels plays a pivotal role in Ca2+ influx, which in turn causes an increase in albumin permeability across the cultured monolayer of porcine pulmonary artery endothelial (PPAE) cells exposed to xanthine/xanthine oxidase (X/XO). Albumin permeability as well as the concentration of intracellular Ca2+ ([Ca2+]i) was increased by X/XO. A H2O2 scavenger (catalase), an iron chelator (o-phenanthroline), and a hydroxyl radical scavenger (dimethyl sulfoxide) inhibited these changes provoked by X/XO, in which intracellular iron-catalyzed hydroxyl radical generation was suggested to be involved. The increase in albumin permeability and [Ca2+]i continued once the PPAE cells were exposed to X/XO. The [Ca2+]i was decreased by a Ca2+ channel blocker, Ni2+, while the removal of Ni2+ increased [Ca2+]i again, suggesting the sustained Ca2+ influx through cell-membrane Ca2+ channels was responsible for the [Ca2+]i elevation. Ni2+ failed to inhibit albumin permeability sustained after the removal of X/XO. In contrast, SH-reducing agents (dithiothreitol and glutathione) inhibited the sustained permeability as well as Ca2+ influx. We concluded that the redox alteration of SH-groups in cell-membrane Ca2+ channels was involved in the increase in albumin permeability after exposure of the endothelial cells to oxidative stress.