Endothelium-dependent hyperpolarization and relaxation resistance to N(G)-nitro-L-arginine and indomethacin in coronary circulation

Zhi-Dong Ge, Xiao Hui Zhang, Peter Chin-Wan Fung, Guo Wei He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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 N(G)-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 (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)547-556
Number of pages10
JournalCardiovascular research
Issue number3
StatePublished - Jun 2000


  • Coronary circulation
  • Endothelial factors
  • K-ATP channel
  • K-channel
  • Membrane potential
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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