Abstract
BackgroundLidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Our aim was to investigate lidocaine’s vasoreactivity properties in intact versus denuded rat thoracic aortic rings, and the effect of inhibitors of nitric oxide (NO), prostenoids, voltage-dependent Kv and KATP channels, membrane Na+/K+ pump, and A2a and A2b receptors.MethodsAortic rings were harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, pH 7.4, 37 °C. The rings were pre-contracted sub-maximally with 0.3 μM norepinephrine (NE), and the effect of increasing lidocaine concentrations was examined. Rings were tested for viability after each experiment with maximally dilating 100 μM papaverine. The drugs 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined.ResultsAll drugs tested had no significant effect on basal tension. Lidocaine relaxation in intact rings was biphasic between 1 and 10 μM (Phase 1) and 10 and 1000 μM (Phase 2). Mechanical removal of the endothelium resulted in further relaxation, and at lower concentrations ring sensitivity (% relaxation per μM lidocaine) significantly increased 3.5 times compared to intact rings. The relaxing factor(s) responsible for enhancing ring relaxation did not appear to be NO- or prostacyclin-dependent, as L-NAME and indomethacin had little or no effect on intact ring relaxation. In denuded rings, lidocaine relaxation was completely abolished by Kv channel inhibition and significantly reduced by antagonists of the MitoKATP channel, and to a lesser extent the SarcKATP channel. Curiously, A2a subtype receptor antagonism significantly inhibited lidocaine relaxation above 100 μM, but not the A2b receptor.ConclusionsWe show that lidocaine relaxation in rat thoracic aorta was biphasic and significantly enhanced by endothelial removal, which did not appear to be NO or prostacyclin dependent. The unknown factor(s) responsible for enhanced relaxation was significantly reduced by Kv inhibition, 5-HD inhibition, and A2a subtype inhibition indicating a potential role for crosstalk in lidocaine’s vasoreactivity.
Highlights
Lidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties
Effect of increasing lidocaine on relaxation in intact and denuded rings Intact rings The gram tension produced with NE administration in endothelium intact rings was not significantly different from denuded aortic rings
We report in isolated rat thoracic rings, precontracted with NE, that lidocaine relaxation was: 1) biphasic from 1 to 10 μM and 10 to 1000 μM, 2) significantly enhanced by endothelial removal, from 1 to 100 μM, 3) not significantly affected in the presence of L-NAME- and indomethacin in intact rings, 4) abolished by 4-AP in denuded rings and significantly reduced by 5-HD, and to a lesser extent glibenclamide, and 5) significantly reduced by A2a subtype antagonist from 100 to 1000 μM, but not A2b
Summary
Lidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Lidocaine is an approved Class 1B antiarrhythmic [2] and exerts anti-inflammatory [3], neuroprotective [4], energy-lowering [5], anti-ischemic [6, 7], anti-oxidant [8, 9] and platelet-neutrophil interactive [10, 11] properties. Lidocaine has been shown to exert a number of vasomodulatory properties in isolated vessels including: 1) endothelium-independent relaxation [12, 13], and 2) vascular smooth muscle relaxation [12, 14, 15] or contraction [15,16,17,18,19] properties. Earlier the same group showed that in precontracted denuded rat aortic rings that acidification promoted lidocaine relaxation and alkanization led to vasoconstriction [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
