title: Effects of lidocaine on rabbit isolated thoracic aorta.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. tn.atd@angelfire.com
authors.forename: N N
authors.initials: NN
authors.lastname: Turan
authors.forename: A T
authors.initials: AT
authors.lastname: Demiryürek
authors.forename: H
authors.initials: H
authors.lastname: Celebi
mesh_terms: 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
chemical_list: D000889:Anti-Arrhythmia Agents; D009566:Nitrates; D014665:Vasodilator Agents; D009599:Nitroprusside; C039642:peroxynitric acid; D008012:Lidocaine