© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Nitroglycerin-mediated vasorelaxation is modulated by endothelial calcium-activated potassium channels
Division of Cardiology, Medical Department B, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
* Corresponding author. Tel.: +45-35-45-23-47; fax: +45-35-45-25-13
Objective: Recent in vitro data suggest, large conductance calcium-activated K+ channels (BKCa) modulate the vascular response to nitric oxide (NO). The in vivo implications and the characteristics of this interaction are not clear. This study firstly investigates whether modulation of BKCa affects the vascular response to nitroglycerin (NTG)-derived NO in vivo and in the isolated heart and secondly examines the influence of endothelial BKCa on NTG-mediated vasodilation in vitro. Methods: The hypotensive effect of NTG was measured in conscious, chronically catheterized rats during i.v. infusions of iberiotoxin (IbTX, a selective inhibitor of BKCa) or placebo. Similarly, NTG-induced flow-changes in the isolated perfused rat heart were examined before and after IbTX treatment (0.1 µM). Concentration-relaxation curves to NTG in the presence of various K+ channel modulating agents were performed in vitro on porcine coronary arteries with and without intact endothelium. Results: I.v. infusion of IbTX reduced the in vivo hypotensive effect of NTG by 55% (before IbTX: 32.0±3.0 mmHg, vs. after IbTX: 14.5±3.2 mmHg, P<0.05) and nearly abolished NTG-induced increase in coronary flow in the isolated perfused heart (P<0.05). In vitro, this effect depended on an intact endothelium (endothelium intact segments; NTG: pD2=5.8±0.1, Emax=97.6±3.2% vs. NTG+IbTX: pD2=4.9±0.2, Emax=49.7±6.2%, P<0.05; endothelium denuded segments; NTG: pD2=6.9±0.1, Emax=104.0±1.4% vs. NTG+IbTX: pD2=6.7±0.1, Emax=100±1.2%, P>0.05). Conclusion: The results suggest, that modulation of endothelial BKCa significantly affects NTG-induced vasorelaxation in vitro, in the isolated perfused heart and in vivo.
KEYWORDS Nitroglycerin; Nitric oxide; Endothelium; Potassium channels; Iberiotoxin
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