Role of potassium channels in endothelium-dependent relaxation resistant to nitroarginine in the rat hepatic artery
Zygmunt, Peter M. LU
and Högestätt, Edward D.
LU
(1996)
In British Journal of Pharmacology
117(7).
p.1600-1606
- Abstract
1. In the presence of indomethacin (IM, 10 μM) and N(ω)-nitro-L-arginine (L-NOARG, 0.3 mM), acetylcholine (ACh) induces an endothelium-dependent smooth muscle hyperpolarization and relaxation in the rat isolated hepatic artery. The potassium (K) channel inhibitors, tetrabutylammonium (TBA, 1 mM) and to a lesser extent 4-aminopyridine (4-AP, 1 mM) inhibited the L-NOARG/IM-resistant relaxation induced by ACh, whereas apamin (0.1-0.3 μM), charybdotoxin (0.1-0.3 μM), iberiotoxin (0.1 μM) and dendrotoxin (0.1 μM) each had no effect. TBA also inhibited the relaxation induced by the receptor-independent endothelial cell activator, A23187. 2. When combined, apamin (0.1 μM)+charybdotoxin (0.1 μM), but not apamin (0.1 μM)+iberiotoxin (0.1 μM) or... (More)
1. In the presence of indomethacin (IM, 10 μM) and N(ω)-nitro-L-arginine (L-NOARG, 0.3 mM), acetylcholine (ACh) induces an endothelium-dependent smooth muscle hyperpolarization and relaxation in the rat isolated hepatic artery. The potassium (K) channel inhibitors, tetrabutylammonium (TBA, 1 mM) and to a lesser extent 4-aminopyridine (4-AP, 1 mM) inhibited the L-NOARG/IM-resistant relaxation induced by ACh, whereas apamin (0.1-0.3 μM), charybdotoxin (0.1-0.3 μM), iberiotoxin (0.1 μM) and dendrotoxin (0.1 μM) each had no effect. TBA also inhibited the relaxation induced by the receptor-independent endothelial cell activator, A23187. 2. When combined, apamin (0.1 μM)+charybdotoxin (0.1 μM), but not apamin (0.1 μM)+iberiotoxin (0.1 μM) or a triple combination of 4-AP (1 mM)+apamin (0.1 μM)+iberiotoxin (0.1 μM), inhibited the L-NOARG/IM-resistant relaxation induced by ACh. At a concentration of 0.3 μM, apamin+charybdotoxin completely inhibited the relaxation. This toxin combination also abolished the L-NOARG/IM-resistant relaxation induced by A23187. 3. In the absence of L-NOARG, TBA (1 mM) inhibited the ACh-induced relaxation, whereas charybdotoxin (0.3 μM)+apamin (0.3 μM) had no effect, indicating that the toxin combination did not interfere with the L-arginine/NO pathway. 4. The gap junction inhibitors halothane (2 mM) and 1-heptanol (2 mM), or replacement of NaCl with sodium propionate did not affect the L-NOARG/IM-resistant relaxation induced by ACh. 5. Inhibition of Na+/K+-ATPase by ouabain (1 mM) had no effect on the L-NOARG/IM-resistant relaxation induced by ACh. Exposure to a K+-free Krebs solution, however, reduced the maximal relaxation by 13% without affecting the sensitivity to ACh. 6. The results suggest that the L-NOARG/IM-resistant relaxation induced by ACh in the rat hepatic artery is mediated by activation of K-channels sensitive to TBA and a combination of apamin+charybdotoxin. Chloride channels, Na+/K+-ATPase and gap junctions are probably not involved in the response. It is proposed that endothelial cell activation induces secretion of an endothelium-derived hyperpolarizing factor(s) (EDHF), distinct from NO and cyclo-oxygenase products, which activates more than one type of K-channel on the smooth muscle cells. Alternatively, a single type of K-channel, to which both apamin and charybdotoxin must bind for inhibition to occur, may be the target for EDHF.
(Less)
- author
- Zygmunt, Peter M.
LU
and Högestätt, Edward D.
LU
- publishing date
- 1996-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Acetylcholine, Arteries, Hyperpolarization, Membrane potential, Nitric oxide, Potassium channels, Vascular endothelium
- in
- British Journal of Pharmacology
- volume
- 117
- issue
- 7
- pages
- 7 pages
- publisher
- Wiley
- external identifiers
-
- scopus:0029912917
- pmid:8730760
- ISSN
- 0007-1188
- DOI
- 10.1111/j.1476-5381.1996.tb15327.x
- language
- English
- LU publication?
- no
- id
- c7db75f1-2beb-4d81-b5d9-751e6af2b57a
- date added to LUP
- 2019-05-31 21:39:52
- date last changed
- 2024-05-28 14:34:19
@article{c7db75f1-2beb-4d81-b5d9-751e6af2b57a,
abstract = {{<p>1. In the presence of indomethacin (IM, 10 μM) and N(ω)-nitro-L-arginine (L-NOARG, 0.3 mM), acetylcholine (ACh) induces an endothelium-dependent smooth muscle hyperpolarization and relaxation in the rat isolated hepatic artery. The potassium (K) channel inhibitors, tetrabutylammonium (TBA, 1 mM) and to a lesser extent 4-aminopyridine (4-AP, 1 mM) inhibited the L-NOARG/IM-resistant relaxation induced by ACh, whereas apamin (0.1-0.3 μM), charybdotoxin (0.1-0.3 μM), iberiotoxin (0.1 μM) and dendrotoxin (0.1 μM) each had no effect. TBA also inhibited the relaxation induced by the receptor-independent endothelial cell activator, A23187. 2. When combined, apamin (0.1 μM)+charybdotoxin (0.1 μM), but not apamin (0.1 μM)+iberiotoxin (0.1 μM) or a triple combination of 4-AP (1 mM)+apamin (0.1 μM)+iberiotoxin (0.1 μM), inhibited the L-NOARG/IM-resistant relaxation induced by ACh. At a concentration of 0.3 μM, apamin+charybdotoxin completely inhibited the relaxation. This toxin combination also abolished the L-NOARG/IM-resistant relaxation induced by A23187. 3. In the absence of L-NOARG, TBA (1 mM) inhibited the ACh-induced relaxation, whereas charybdotoxin (0.3 μM)+apamin (0.3 μM) had no effect, indicating that the toxin combination did not interfere with the L-arginine/NO pathway. 4. The gap junction inhibitors halothane (2 mM) and 1-heptanol (2 mM), or replacement of NaCl with sodium propionate did not affect the L-NOARG/IM-resistant relaxation induced by ACh. 5. Inhibition of Na<sup>+</sup>/K<sup>+</sup>-ATPase by ouabain (1 mM) had no effect on the L-NOARG/IM-resistant relaxation induced by ACh. Exposure to a K<sup>+</sup>-free Krebs solution, however, reduced the maximal relaxation by 13% without affecting the sensitivity to ACh. 6. The results suggest that the L-NOARG/IM-resistant relaxation induced by ACh in the rat hepatic artery is mediated by activation of K-channels sensitive to TBA and a combination of apamin+charybdotoxin. Chloride channels, Na<sup>+</sup>/K<sup>+</sup>-ATPase and gap junctions are probably not involved in the response. It is proposed that endothelial cell activation induces secretion of an endothelium-derived hyperpolarizing factor(s) (EDHF), distinct from NO and cyclo-oxygenase products, which activates more than one type of K-channel on the smooth muscle cells. Alternatively, a single type of K-channel, to which both apamin and charybdotoxin must bind for inhibition to occur, may be the target for EDHF.</p>}},
author = {{Zygmunt, Peter M. and Högestätt, Edward D.}},
issn = {{0007-1188}},
keywords = {{Acetylcholine; Arteries; Hyperpolarization; Membrane potential; Nitric oxide; Potassium channels; Vascular endothelium}},
language = {{eng}},
month = {{01}},
number = {{7}},
pages = {{1600--1606}},
publisher = {{Wiley}},
series = {{British Journal of Pharmacology}},
title = {{Role of potassium channels in endothelium-dependent relaxation resistant to nitroarginine in the rat hepatic artery}},
url = {{http://dx.doi.org/10.1111/j.1476-5381.1996.tb15327.x}},
doi = {{10.1111/j.1476-5381.1996.tb15327.x}},
volume = {{117}},
year = {{1996}},
}