© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Endothelium-dependent hyperpolarization and relaxation resistance to NG-nitro-L-arginine and indomethacin in coronary circulation
aCardiovascular Research Laboratory, Grantham Hospital, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
bDivision of Medical Physics, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China
cCardiovascular Research, Albert Starr Academic Center for Cardiac Surgery, St. Vincent Hospital, Portland, Oregon, USA
* Corresponding author. Professor G.-W. He, Chair of Cardiothoracic Surgery, University of Hong Kong, Grantham Hospital, 125 Wong Chuk Hang Road, Aberdeen, Hong Kong. Tel.: +852-2518-2631; fax: +852-2814-8635 gwhe{at}hkucc.hku.hk
Objective: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to NG-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. Methods: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. Results: In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5±2.4 nM to 105.0±19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1±11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from –51±3 mV to –30±4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2±5.7%) and repolarization (membrane potential: –50±4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3±4.4%) and repolarization (-40±2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization. Conclusions: In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BKCa) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as ‘backup’ mechanisms when BKCa is curtailed.
KEYWORDS Coronary circulation; Endothelial factors; K-ATP channel; K-channel; Membrane potential; Nitric oxide
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