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Endothelium‐dependent relaxation to acetylcholine in the rabbit basilar artery: importance of membrane hyperpolarization
Author(s) -
Rand Victoria E.,
Garland C.J.
Publication year - 1992
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.1476-5381.1992.tb14307.x
Subject(s) - hyperpolarization (physics) , acetylcholine , membrane potential , chemistry , medicine , endocrinology , biophysics , muscarinic acetylcholine receptor , biochemistry , biology , stereochemistry , receptor , nuclear magnetic resonance spectroscopy
1 Muscarinic stimulation of isolated, preconstricted segments of the basilar artery, with either acetylcholine or carbachol, was followed by endothelium‐dependent smooth muscle relaxation and membrane hyperpolarization. 2 Smooth muscle relaxation to acetylcholine was stimulated in the presence of lower concentrations than the associated hyperpolarization (EC 50 values 3.2 μ m and 31.6 μ m , respectively), and was sustained during agonist application, while the hyperpolarization was relatively transient. 3 Repeated exposure to acetylcholine was associated with loss of membrane hyperpolarization, while smooth muscle relaxation was unaltered. Following a second exposure to 100 μ m acetylcholine, mean hyperpolarization was markedly depressed from 8.5 to 2 mV, and subsequent exposures failed to induce any hyperpolarization. Relaxations with a similar amplitude and rate of development, were recorded with each subsequent addition of acetylcholine. 4 The competitive substrate inhibitors for nitric oxide synthase, l ‐N G ‐monomethyl arginine (100 μ m l ‐NMMA) or l ‐N G ‐nitro arginine methyl ester (100 μ m l ‐NAME), modified the form and amplitude of both the relaxation and the hyperpolarization to acetylcholine. In the majority of experiments, both the hyperpolarization and the relaxation were almost totally abolished. 5 Neither nitric oxide, applied directly in physiological salt solution, nor sodium nitroprusside, produced smooth muscle hyperpolarization except in high concentrations. Reproducible, small amplitude (around 2 mV) hyperpolarization followed the application of either NO gas (15 μ m ) or sodium nitroprusside (100 μ m ), both of which induced almost maximal smooth muscle relaxation. 6 These data show that muscarinic stimulation of endothelial cells in the rabbit basilar artery is followed by both smooth muscle hyperpolarization and relaxation. They indicate that nitric oxide is involved in both of these responses, but that the smooth muscle hyperpolarization is not an essential component of the relaxation.