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Differences in the K + ‐channels opened by cromakalim, acetylcholine and substance P in rat aorta and porcine coronary artery
Author(s) -
Bray Katharine,
Quast Ulrich
Publication year - 1991
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.1476-5381.1991.tb12217.x
Subject(s) - cromakalim , acetylcholine , glibenclamide , tetraethylammonium , chemistry , efflux , phenylephrine , endocrinology , medicine , apamin , potassium channel , aorta , pharmacology , endothelium , biochemistry , potassium , biology , organic chemistry , blood pressure , diabetes mellitus
1 The effects of acetylcholine and substance P on the efflux of 86 Rb + and 42 K + from rat aorta and pig coronary artery, respectively, were compared with those of the K + channel opening agent, cromakalim. 2 In rat aorta preloaded with 86 Rb + and/or 42 K + , acetylcholine produced transient, concentration‐dependent increases in the efflux rate coefficients of these tracers (maximum ≅ 35%). These effects were abolished by endothelial cell removal. 3 Donor/acceptor experiments with rat aorta suggested that at least some of the efflux of 86 Rb + seen in the presence of acetylcholine was not derived from the endothelium, but came from the smooth muscle itself. 4 Acetylcholine (10 μ m )‐induced 86 Rb + efflux was reduced by tetraethylammonium (TEA, 10 m m ) to 33% and ouabain (300 μ m ) to 54% of control. Preincubation with Ba 2+ (100 μ m ) did not significantly inhibit acetylcholine‐induced efflux. 5 Acetylcholine‐induced 42 K + / 86 Rb + efflux was unaffected by preincubation with glibenclamide (10 μ m ). In contrast, the 42 K + / 86 Rb + efflux induced by cromakalim was inhibited by glibenclamide (50 n m ) by 50%. 6 Acetylcholine (0.3–10 μ m )‐induced inhibition of phenylephrine (1 μ m )‐induced tone was abolished by endothelial cell removal but unaffected by glibenclamide. Cromakalim‐induced relaxations were endothelium‐independent and were inhibited by glibenclamide in a concentration‐dependent manner. 7 l G ‐monomethyl l ‐arginine ( l ‐NMMA, 250 μ m ) produced a significant (37 ± 14%) inhibition of acetylcholine‐induced 86 Rb + efflux whereas D G ‐monomethyl l ‐arginine was without effect. In the tissue bath l ‐NMMA inhibited relaxations produced by acetylcholine (0.3–10 μ m ), but was without effect on responses to cromakalim. 8 In the pig coronary artery, substance P induced an endothelium‐dependent efflux of 86 Rb + and 42 K + , which was unaffected by preincubation with glibenclamide (10 μ m ) or l ‐NMMA (250 μ m ). 9 The present study shows that acetylcholine and substance P each open K + ‐channels in arterial smooth muscle. However, the insensitivity of the stimulated 86 Rb + / 42 K + efflux to inhibition by glibenclamide suggests that the K + ‐channel opened by these agents is different from the K + ‐channel opened by cromakalim. In addition, the inability of l ‐NMMA to inhibit fully the acetylcholine‐ and substance P‐stimulated 86 Rb + efflux suggests that in rat aorta and pig coronary artery the endothelium‐derived hyperpolarizing factor(s) (EDHF) is different from endothelium‐derived relaxing factor (EDRF).