Effects of lidocaine on rabbit isolated thoracic aorta.
Lidocaine has been demonstrated to modify both contraction and relaxation of the vascular smooth muscle. Although lidocaine has been shown to inhibit endothelium-independent relaxations, the effects of lidocaine on arterial relaxation induced by peroxynitrite, a reaction product of superoxide and nitric oxide, have not been studied. The current study was designed to evaluate the effects of lidocaine on endothelium-dependent and -independent relaxations in isolated rabbit thoracic aorta. Rings of the rabbit thoracic aorta with or without endothelium were mounted for isometric force recording. Concentration-response curves to calcium ionophore A23187 ( 10(-9)to 3 x 10(-6)m), acetylcholine ( 10(-9)to 10(-3)m), sodium nitroprusside (SNP, 10(-9)to 10(-3)m), and peroxynitrite ( 10(-9)to 10(-3)m) were obtained in a cumulative manner. Lidocaine ( 10(-6)to 10(-4)m) was applied 15 min before addition of phenylephrine. Under resting force, lidocaine produced contractions at high concentrations ( 10(-5)to 10(-2)m) in endothelium-intact and -denuded arteries but removal of the endothelium did not significantly affect contractile activity. In phenylephrine-precontracted arteries, lidocaine caused concentration-dependent relaxations in both endothelium-intact and -denuded arteries. Inhibition of nitric oxide synthase or removal of endothelium did not affect the relaxations to lidocaine. Lidocaine suppressed the endothelium-independent relaxations of peroxynitrite, also poly (ADP-ribose) synthetase (PARS) enzyme activator, and SNP at high concentrations. Concentration-dependent vascular relaxations to A23187 and acetylcholine were significantly inhibited by lidocaine. These results suggest that lidocaine can depress vascular relaxations by a complex mechanism including inhibition of PARS enzyme activity.
Turan
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Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. tn.atd@angelfire.com
Demiryürek
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Celebi
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D008012:Lidocaine / Q000494:pharmacology*; D009566:Nitrates / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D009566:Nitrates; D014665:Vasodilator Agents; D009599:Nitroprusside; C039642:peroxynitric acid; D008012:Lidocaine