Apamin-sensitive K + channels involved in the inhibition of acetylcholine-induced contractions in lamb coronary small arteries

• Published in: European journal of pharmacology Vol. 329; no. 2; pp. 153 - 163
• Main Authors: Simonsen, Ulf, García-Sacristán, Albino, Prieto, Dolores
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.06.1997; Elsevier
• Subjects: A23187; Acetylcholine; Acetylcholine - pharmacology; Animals; Apamin; Apamin - pharmacology; Arginine - antagonists & inhibitors; Biological and medical sciences; Blood vessels and receptors; Calcimycin - pharmacology; Calcium - metabolism; Coronary small artery; Coronary Vessels - drug effects; Coronary Vessels - physiology; Cyclooxygenase Inhibitors - pharmacology; Endothelium; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Indomethacin - pharmacology; Ionophores - pharmacology; K + channel; Muscarinic Antagonists - pharmacology; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Nitric oxide (NO); Nitric Oxide - antagonists & inhibitors; Nitric Oxide - pharmacology; Potassium Channel Blockers; Potassium Channels - physiology; Sheep; Vertebrates: cardiovascular system; Apamin; Coronary small artery; K + channel; Acetylcholine; A23187; Nitric oxide (NO); Endothelium; Coronary artery; Vasoconstriction; Smooth muscle; Ionic channel; Muscle contraction; In vitro; Neuromodulation; M1 receptor; Lamb; Mechanism; Vertebrata; Regulation(control); Mammalia; Animal; Nitric oxide; Blood vessel; Neurotransmitter; Sheep; Artiodactyla; Circulatory system; Potassium; Ungulata
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)89177-7

In vitro experiments were designed to investigate the endothelial factors involved in modulation of the contractile response to acetylcholine in lamb coronary small arteries. Endothelial cell removal. and inhibitors of the l-arginine/nitric oxide (NO) pathway increased basal tension and contractions in response to acetylcholine and abolished relaxations in response to the Ca 2+-ionophore, 6 S-[6α(2 S∗,3 S∗),8β( R∗),9β,11α]-5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1 H-pyrrol-2-yl)ethyl]-1,7-di acid (A23187). N G-Nitro- l-marginine enhanced acetylcholine-induced contractions in the absence, but not in the presence of the muscarinic M 1 receptor antagonist, telenzepine. In contrast to glibenclamide and charybdotoxin, apamin enhanced the acetylcholine-induced contractions and reduced the relaxations caused by A23187 and exogenously added NO. The combination of 1 H-[1,2,4]oxadiazolo[4,3,- a]quinoxalin-l-one (ODQ) and apamin did not further increase the acetylcholine-induced contractions. These results indicate that muscarinic M 1 receptor-released endothelial NO inhibits the contractile responses to acetylcholine in lamb coronary small arteries through activation of guanylate cyclase, followed by an increase in apamin-sensitive K + conductance of the smooth muscle.