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Endothelium‐derived factors and hyperpolarization of the carotid artery of the guinea‐pig
Author(s) -
Corriu Catherine,
Félétou Michel,
Canet Emmanuel,
Vanhoutte Paul M.
Publication year - 1996
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 - 10.1111/j.1476-5381.1996.tb15765.x
Subject(s) - apamin , hyperpolarization (physics) , charybdotoxin , chemistry , acetylcholine , endocrinology , medicine , membrane potential , pharmacology , biophysics , biochemistry , potassium channel , stereochemistry , biology , nuclear magnetic resonance spectroscopy
1 Transmembrane potentials were recorded from isolated carotid arteries of the guinea‐pig supervised with modified Krebs‐Ringer bicarbonate solution. Smooth muscle cells were impaled from the adventitial side with intracellular glass microelectrodes filled with KCl (30–80 MΩ). 2 Acetylcholine (1 μ m ) in the presence of inhibitors of nitric oxide synthase, (N ω ‐nitro‐L‐arginine (L‐NOARG) 100 μ m ) and cyclo‐oxygenase, (indomethacin 5 μ m ) induced an endothelium‐dependent hyperpolarization (−18.9±1.6 mV, n = 15). 3 In the presence of these two inhibitors, S‐nitroso‐L‐glutathione (10 μ m ), sodium nitroprusside (10 μ m ), 3‐morphohnosydnonimine (SIN‐1, 10 μ m ) and iloprost (0.1 μ m ) induced endothelium‐independent hyperpolarizations of the smooth muscle cells (respectively: −16.0±2.3, −16.3±3.4, −12.8±2.0 and −14.5±1.5 mV, n = 4–6). 4 The addition of glibenclamide (1 μ m ) did not influence the acetylcholine‐induced L‐NOARG/indomethacin‐resistant hyperpolarization (−18.0 ± 1.8 mV, n = 10). In contrast, the responses induced by S‐nitroso‐L‐glutathione, sodium nitroprusside, SIN‐1 and iloprost were abolished (changes in membrane potential: −0.8 ± 1.1, 1.3 ± 3.9, 4.5 ± 4.6 and 0.3 ± 0.8 mV respectively, n = 4–5). 5 In the presence of NO synthase and cyclo‐oxygenase inhibitors, charybdotoxin (0.1 μ m ) or apamin (0.5 μ m ) did not influence the hyperpolarization produced by acetylcholine. However, in the presence of the combination of charybdotoxin and apamin, the acetylcholine‐induced L‐NOARG/indomethacin‐resistant hyperpolarization was converted to a depolarization (4.4 ± 1.2mV, n = 20) while the endothelium‐independent hyperpolarizations induced by S‐nitroso‐L‐glutathione, sodium nitroprusside, SIN‐1 and iloprost were not affected significantly (respectively: −20.4 ± 3.4, −22.5 ± 4.9, −14.5 ± 4.7 and −14.5 ± 0.5mV, n = 4–5). 6 In the presence of the combination of charybdotoxin and apamin and in the absence of L‐NOARG and indomethacin, acetylcholine induced a hyperpolarization (−19.5 ± 3.7 mV, n = 4). This hyperpolarization induced by acetylcholine was not affected by the addition of indomethacin (−18.3 ± 4.6 mV, n = 3). In the presence of the combination of charybdotoxin, apamin and L‐NOARG (in the absence of indomethacin), acetylcholine, in 5 out of 7 vessels, still produced hyperpolarization which was not significantly smaller (−9.1 ± 5.6 mV, n = 7) than the one observed in the absence of L‐NOARG. 7 These findings suggest that, in the guinea‐pig isolated carotid artery, the endothelium‐independent hyperpolarizations induced by NO donors and iloprost involve the opening of K ATP channels while the acetylcholine‐induced endothelium‐dependent hyperpolarization (resistant to the inhibition of NO‐synthase and cyclo‐oxygenase) involves the opening of Ca 2+ ‐activated potassium channel(s). Furthermore, in this tissue, acetylcholine induces the simultaneous release of various factors from endothelial origin: hyperpolarizing factors (NO, endothelium derived hyperpolarizing factor (EDHF) and prostaglandins) and possibly a depolarizing factor.