Differences in the K+‐channels opened by cromakalim, acetylcholine and substance P in rat aorta and porcine coronary artery

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Abstract
1 The effects of acetylcholine and substance P on the efflux of 86Rb+ and 42K+ 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 86Rb+ and/or 42K+, 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 86Rb+ seen in the presence of acetylcholine was not derived from the endothelium, but came from the smooth muscle itself. 4 Acetylcholine (10 μm)-induced 86Rb+ efflux was reduced by tetraethylammonium (TEA, 10 mm) to 33% and ouabain (300 μm) to 54% of control. Preincubation with Ba2+ (100 μm) did not significantly inhibit acetylcholine-induced efflux. 5 Acetylcholine-induced 42K+/86Rb+ efflux was unaffected by preincubation with glibenclamide (10 μm). In contrast, the 42K+/86Rb+ efflux induced by cromakalim was inhibited by glibenclamide (50 nm) by 50%. 6 Acetylcholine (0.3–10 μm)-induced inhibition of phenylephrine (1 μm)-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 lG-monomethyl l-arginine (l-NMMA, 250 μm) produced a significant (37 ± 14%) inhibition of acetylcholine-induced 86Rb+ efflux whereas DG-monomethyl l-arginine was without effect. In the tissue bath l-NMMA inhibited relaxations produced by acetylcholine (0.3–10 μm), but was without effect on responses to cromakalim. 8 In the pig coronary artery, substance P induced an endothelium-dependent efflux of 86Rb+ and 42K+, which was unaffected by preincubation with glibenclamide (10 μm) or l-NMMA (250 μm). 9 The present study shows that acetylcholine and substance P each open K+-channels in arterial smooth muscle. However, the insensitivity of the stimulated 86Rb+/42K+ 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 86Rb+ 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).