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Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries
Author(s) -
Matchkov Vladimir V,
Rahman Awahan,
Peng Hongli,
Nilsson Holger,
Aalkjær Christian
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705870
Subject(s) - heptanol , gap junction , electrical impedance myography , chemistry , vasodilation , biophysics , anatomy , mesenteric arteries , isometric exercise , vascular smooth muscle , membrane potential , intracellular , electrophysiology , biochemistry , biology , medicine , artery , endocrinology , smooth muscle
Heptanol, 18 α ‐glycyrrhetinic acid (18 α GA) and 18 β ‐glycyrrhetinic acid (18 β GA) are known blockers of gap junctions, and are often used in vascular studies. However, actions unrelated to gap junction block have been repeatedly suggested in the literature for these compounds. We report here the findings from a comprehensive study of these compounds in the arterial wall. Rat isolated mesenteric small arteries were studied with respect to isometric tension (myography), [Ca 2+ ] i (Ca 2+ ‐sensitive dyes), membrane potential and – as a measure of intercellular coupling – input resistance (sharp intracellular glass electrodes). Also, membrane currents (patch‐clamp) were measured in isolated smooth muscle cells (SMCs). Confocal imaging was used for visualisation of [Ca 2+ ] i events in single SMCs in the arterial wall. Heptanol (150 μ M ) activated potassium currents, hyperpolarised the membrane, inhibited the Ca 2+ current, and reduced [Ca 2+ ] i and tension, but had little effect on input resistance. Only at concentrations above 200 μ M did heptanol elevate input resistance, desynchronise SMCs and abolish vasomotion. 18 β GA (30 μ M ) not only increased input resistance and desynchronised SMCs but also had nonjunctional effects on membrane currents. 18 α GA (100 μ M ) had no significant effects on tension, [Ca 2+ ] i , total membrane current and synchronisation in vascular smooth muscle. We conclude that in mesenteric small arteries, heptanol and 18 β GA have important nonjunctional effects at concentrations where they have little or no effect on intercellular communication. Thus, the effects of heptanol and 18 β GA on vascular function cannot be interpreted as being caused only by effects on gap junctions. 18 α GA apparently does not block communication between SMCs in these arteries, although an effect on myoendothelial gap junctions cannot be excluded.British Journal of Pharmacology (2004) 142 , 961–972. doi: 10.1038/sj.bjp.0705870