Premium
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
Author(s) -
Andersson David A,
Zygmunt Peter M,
Movahed Pouya,
Andersson Tomas L G,
Högestätt Edward D
Publication year - 2000
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.0703226
Subject(s) - apamin , charybdotoxin , chemistry , potassium channel , tetraethylammonium , ouabain , calcium , calcium activated potassium channel , potassium channel blocker , biophysics , potassium , medicine , biochemistry , endocrinology , stereochemistry , membrane potential , sodium , biology , organic chemistry
In the rat hepatic artery, the SK Ca inhibitors UCL 1684 (300 n M ) completely blocked, and scyllatoxin (1 μ M ) and d‐tubocurarine (100 μ M ) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 n M ). The IK Ca inhibitors clotrimazole (3 μ M ) and 2‐chlorophenyl‐bisphenyl‐methanol (3 μ M ) strongly depressed EDHF relaxations when each of them was combined with apamin (300 n M ). The cytochrome P450 mono‐oxygenase inhibitor ketoconazole (10 μ M ) had no effect in the presence of apamin. Ciclazindol (10 μ M ), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated 86 Rb + influx via the Gardos channel (IK Ca ) in human erythrocytes. The Na + /K + ATPase inhibitor ouabain (500 μ M ) and the K IR blocker Ba 2+ (30 μ M ) neither alone nor in combination inhibited EDHF relaxations. Ba 2+ was also without effect in the presence of either apamin or charybdotoxin. In contrast to EDHF, an increase in extracellular [K + ] from 4.6 m M to 9.6, 14.6 and 19.6 m M 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 Ba 2+ . 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.British Journal of Pharmacology (2000) 129 , 1490–1496; doi: 10.1038/sj.bjp.0703226