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Effects of large conductance Ca(2+)-activated K(+) channels on nitroglycerin-mediated vasorelaxation in humans

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Nicolai Gruhn
  • Søren Boesgaard
  • Eiberg, Jonas Peter
  • Lone Bang
  • Jens Thiis
  • Torben V Schroeder
  • Jan Aldershvile
Nitric oxide (NO)-induced vasorelaxation and the regulation of endothelial superoxide anion levels is partly mediated by vascular large conductance Ca(2+)-activated K(+) (BK(Ca)) channels. Nitroglycerin acts through the release of NO and its effect is modulated by changes in endothelial superoxide levels. This study examines the effect of BK(Ca) channel blockade on nitroglycerin-induced vasorelaxation in human arterial and venous vascular segments and whether responses to BK(Ca) channel blockade are influenced by the development of venous nitroglycerin tolerance. Dose-relaxation curves to nitroglycerin (10(-10)-10(-4) M) were obtained in segments of the saphenous vein and the left mammary artery. Studies were performed with and without pre-incubation with the BK(Ca) channel blocker iberiotoxin (10(-7) M) and venous tolerance to nitroglycerin were induced by a 24-h i.v. infusion (0.5 microg/kg/min). Iberiotoxin reduced the vasorelaxant effect of nitroglycerin (E(max)) by 60% in endothelium-intact arteries and 13% in endothelium-denuded arteries (P0.05) and (compared to arterial segments) veins were less sensitive to BK(Ca) channel blockade (30% reduction in E(max)) or endothelial removal. The results suggest that primarily arterial effects of nitroglycerin are significantly inhibited by changes in the activity of the endothelial BK(Ca) channels. Although endothelial BK(Ca) are likely regulators of mechanisms underlying arterial tolerance development to nitroglycerin, they do not appear to play a role in human venous nitroglycerin tolerance development.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Pharmacology
Vol/bind446
Udgave nummer1-3
Sider (fra-til)145-50
Antal sider6
ISSN0014-2999
StatusUdgivet - 20 jun. 2002

ID: 34045307