Effects of lidocaine on rabbit isolated thoracic aorta


Turan N., Demiryurek A., Celebi H.

PHARMACOLOGICAL RESEARCH, vol.42, no.5, pp.453-458, 2000 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 42 Issue: 5
  • Publication Date: 2000
  • Doi Number: 10.1006/phrs.2000.0729
  • Title of Journal : PHARMACOLOGICAL RESEARCH
  • Page Numbers: pp.453-458

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)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. (C) 2000 Academic Press.