Effects of large conductance Ca(2+)-activated K(+) channels on nitroglycerin-mediated vasorelaxation in humans
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Effects of large conductance Ca(2+)-activated K(+) channels on nitroglycerin-mediated vasorelaxation in humans. / Gruhn, Nicolai; Boesgaard, Søren; Eiberg, Jonas; Bang, Lone; Thiis, Jens; Schroeder, Torben V; Aldershvile, Jan.
I: European Journal of Pharmacology, Bind 446, Nr. 1-3, 20.06.2002, s. 145-50.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Effects of large conductance Ca(2+)-activated K(+) channels on nitroglycerin-mediated vasorelaxation in humans
AU - Gruhn, Nicolai
AU - Boesgaard, Søren
AU - Eiberg, Jonas
AU - Bang, Lone
AU - Thiis, Jens
AU - Schroeder, Torben V
AU - Aldershvile, Jan
PY - 2002/6/20
Y1 - 2002/6/20
N2 - 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.
AB - 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.
M3 - Journal article
VL - 446
SP - 145
EP - 150
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -
ID: 34045307