Advanced

Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na+/K+ ATPase on EDHF relaxations in the rat hepatic artery

Andersson, David A. LU ; Zygmunt, Peter M. LU ; Movahed, Pouya LU ; Andersson, Tomas L.G. LU and Högestätt, Edward D. LU (2000) In British Journal of Pharmacology 129(7). p.1490-1496
Abstract

1. In the rat hepatic artery, the SK(Ca) inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 μM) and d-tubocurarine (100 μM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). 2. The IK(Ca) inhibitors clotrimazole (3 μM) and 2-chlorophenyl-bisphenyl-methanol (3 μM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 μM) had no effect in the presence of apamin. 3. Ciclazindol (10 μM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated 86Rb+ influx via the Gardos channel (IK(Ca))... (More)

1. In the rat hepatic artery, the SK(Ca) inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 μM) and d-tubocurarine (100 μM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). 2. The IK(Ca) inhibitors clotrimazole (3 μM) and 2-chlorophenyl-bisphenyl-methanol (3 μM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 μM) had no effect in the presence of apamin. 3. Ciclazindol (10 μM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated 86Rb+ influx via the Gardos channel (IK(Ca)) in human erythrocytes. 4. The Na(+/)K+ ATPase inhibitor ouabain (500 μM) and the K(IR) blocker Ba2+ (30 μM) neither alone nor in combination inhibited EDHF relaxations. Ba2+ was also without effect in the presence of either apamin or charybdotoxin. 5. In contrast to EDHF, an increase in extracellular [K+] from 4.6 mM to 9.6, 14.6 and 19.6 mM inconsistently relaxed arteries. In K+-free physiological salt solution, re-admission of K+ always caused complete and sustained relaxations which were abolished by ouabain but unaffected by Ba2+. 6. The present study provides pharmacological evidence for the involvement of SK(Ca) and IK(Ca) in the action of EDHF in the rat hepatic artery. Our results are not consistent with the idea that EDHF is K+ activating Na+/K+ ATPase and K(IR) in this blood vessel.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Blood vessels, Endothelium vascular, Endothelium-derived relaxing factor, Potassium channels
in
British Journal of Pharmacology
volume
129
issue
7
pages
7 pages
publisher
The British Pharmacological Society
external identifiers
  • scopus:0034101057
  • pmid:10742306
ISSN
0007-1188
DOI
10.1038/sj.bjp.0703226
language
English
LU publication?
yes
id
94b68ce1-dfee-4c0f-b02f-eaf8896309af
date added to LUP
2019-05-31 21:35:07
date last changed
2019-12-03 02:12:03
@article{94b68ce1-dfee-4c0f-b02f-eaf8896309af,
  abstract     = {<p>1. In the rat hepatic artery, the SK(Ca) inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 μM) and d-tubocurarine (100 μM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). 2. The IK(Ca) inhibitors clotrimazole (3 μM) and 2-chlorophenyl-bisphenyl-methanol (3 μM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 μM) had no effect in the presence of apamin. 3. Ciclazindol (10 μM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated <sup>86</sup>Rb<sup>+</sup> influx via the Gardos channel (IK(Ca)) in human erythrocytes. 4. The Na(+/)K<sup>+</sup> ATPase inhibitor ouabain (500 μM) and the K(IR) blocker Ba<sup>2+</sup> (30 μM) neither alone nor in combination inhibited EDHF relaxations. Ba<sup>2+</sup> was also without effect in the presence of either apamin or charybdotoxin. 5. In contrast to EDHF, an increase in extracellular [K<sup>+</sup>] from 4.6 mM to 9.6, 14.6 and 19.6 mM inconsistently relaxed arteries. In K<sup>+</sup>-free physiological salt solution, re-admission of K<sup>+</sup> always caused complete and sustained relaxations which were abolished by ouabain but unaffected by Ba<sup>2+</sup>. 6. The present study provides pharmacological evidence for the involvement of SK(Ca) and IK(Ca) in the action of EDHF in the rat hepatic artery. Our results are not consistent with the idea that EDHF is K<sup>+</sup> activating Na<sup>+</sup>/K<sup>+</sup> ATPase and K(IR) in this blood vessel.</p>},
  author       = {Andersson, David A. and Zygmunt, Peter M. and Movahed, Pouya and Andersson, Tomas L.G. and Högestätt, Edward D.},
  issn         = {0007-1188},
  language     = {eng},
  month        = {01},
  number       = {7},
  pages        = {1490--1496},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na<sup>+</sup>/K<sup>+</sup> ATPase on EDHF relaxations in the rat hepatic artery},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0703226},
  doi          = {10.1038/sj.bjp.0703226},
  volume       = {129},
  year         = {2000},
}