Inhibition of Nitric Oxide-Induced Vasodilation by Gap Junction Inhibitors: A Potential Role for a cGMP-Independent Nitric Oxide Pathway

Patrick J. Javid, Stephanie W. Watts, R Clinton Webb

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Studies have provided evidence for the role of gap junctional intercellular communication in syncytial tissue function. This study tested the hypothesis that the vasodilating effects of nitric oxide (NO) rely on gap junctions. The effects of the gap junction inhibitors octanol (10-4 mol/l) and heptanol (10-3 mol/l) were examined on acetylcholine-, the NO-donor S-nitroso-N-acetyl-penicillamine (SNAP)-, and guanosine-3’, 5’-cyclic monophosphate (cGMP)-induced relaxation. In addition, we tested varying concentrations of the gap junction inhibitor sucrose on SNAP-induced relaxation in the presence and absence of methylene blue, an inhibitor of guanylate cyclase. Helical strips of rat thoracic aorta were placed in muscle baths for isometric force measurements. Tissues treated with SNAP and cGMP were denuded of endothelium. Tissues incubated in octanol and heptanol exhibited 4- to 7-fold rightward shifts in acetylcholine-induced and 6- to 15-fold rightward shifts in SNAP-induced relaxation. Both octanol and heptanol produced 2-fold rightward shifts in cGMP-induced relaxation, comparably less in magnitude than shifts produced in acetylcholine- and SNAP-induced relaxation. Sucrose (10-2 to 10-1 mol/l) produced a concentration-dependent rightward shift of up to 30-fold in relaxation to SNAP. Incubation with methylene blue (10-6 mol/l) altered this rightward shift only slightly, indicating a possible cGMP-indepen-dent mechanism for NO. These findings support the hypothesis that NO-induced vasodilation, through both cGMP-dependent and -independent pathways, relies on gap junctional communication.

Original languageEnglish (US)
Pages (from-to)395-404
Number of pages10
JournalJournal of Vascular Research
Volume33
Issue number5
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • Acetylcholine
  • cGMP
  • Gap junctions
  • Heptanol
  • Nitric oxide
  • Octanol
  • Sucrose
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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