© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Nitric oxide mediated endothelium-dependent relaxation induced by glibenclamide in rat isolated aorta
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong, People’s Republic of China
* Corresponding author. Tel.: +852-2-609-6787; fax: +852-2-603-5022 yu-huang{at}cuhk.edu.hk
Objectives: Glibenclamide was found to act as both a selective ATP-sensitive K+ channel blocker and a vasorelaxant. The exact mechanisms underlying the relaxant effect of glibenclamide are unknown. The present study was designed to examine the role of endothelium/nitric oxide in glibenclamide-induced relaxation in rat isolated aortic rings. Methods: A combination of experimental approaches including isometric force measurement, cell culture, Ca2+ fluorescence measurement and radioimmunoassay were used to examine the vascular effect of glibenclamide. Results: Glibenclamide induced a concentration-dependent relaxation more effectively in rings with endothelium (IC50 of 32±4 µM) than those without endothelium (IC50 of 365±29 µM). Incubation with NG-nitro-L-arginine methyl ester (L-NAME) or methylene blue significantly reduced and L-arginine (3 mM) potentiated the glibenclamide-induced relaxation. L-Arginine (3 mM) partially antagonized the effect of L-NAME. Glibenclamide (100 µM) increased the cyclic GMP content of endothelium-intact tissues. Pretreatment with NG-nitro-L-arginine (100 µM) or removal of endothelium significantly suppressed the effect of glibenclamide on cyclic GMP production. Glibenclamide elevated the intracellular Ca2+ levels in cultured rat aortic endothelial cells. Glibenclamide also inhibited the endothelium-independent contractile response to 60 mM K+ (IC50 of 137±21 µM) and caused a rightward shift in the concentration–contraction curve for CaCl2. Besides, glibenclamide inhibited phorbol-12,13-diacetate (1 µM)-induced contraction in Ca2+-free Krebs solution. Conclusion: These results indicate that glibenclamide-induced endothelium-dependent relaxation involves nitric oxide release and this effect may be related to its stimulatory effect on endothelial Ca2+ levels. However, the glibenclamide-induced endothelium-independent relaxation may be associated with its inhibitory effect on Ca2+ influx through Ca2+ channels and on the protein kinase C-mediated contractile mechanism.
KEYWORDS Arteries; Ca-channel; Endothelial function; K-ATP channel; Nitric oxide; Vasoconstriction/dilation
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Moritz, R. Gust, and H. H. Pertz Characterization of the Relaxant Response to N,N'-Dipropyl-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine in Porcine Coronary Arteries J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 699 - 706. [Abstract] [Full Text] [PDF]
|
|