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The John B. Pierce Laboratory and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06519
Endothelial
cells are considered electrically unexcitable. However,
endothelium-dependent vasodilators (e.g., acetylcholine) often evoke
hyperpolarization. We hypothesized that electrical stimulation of
endothelial cells could evoke hyperpolarization and vasodilation. Feed
artery segments (resting diameter: 63 ± 1 µm; length 3-4
mm) of the hamster retractor muscle were isolated and pressurized to 75 mmHg, and focal stimulation was performed via microelectrodes
positioned across one end of the vessel. Stimulation at 16 Hz
(30-50 V, 1-ms pulses, 5 s) evoked constriction (
20 ± 2 µm) that spread along the entire vessel via perivascular
sympathetic nerves, as shown by inhibition with tetrodotoxin,
-conotoxin, or phentolamine. In contrast, stimulation with direct
current (30 V, 5 s) evoked vasodilation (16 ± 2 µm) and
hyperpolarization (11 ± 1 mV) of endothelial and smooth muscle
cells that conducted along the entire vessel. Conducted responses were
insensitive to preceding treatments, atropine, or
N
-nitro-L-arginine, yet were
abolished by endothelial cell damage (with air). Injection of negative
current (
1.6 nA) into a single endothelial cell reproduced
vasodilator responses along the entire vessel. We conclude that,
independent of ligand-receptor interactions, endothelial cell
hyperpolarization evokes vasodilation that is readily conducted along
the vessel wall. Moreover, electrical events originating within a
single endothelial cell can drive the relaxation of smooth muscle cells
throughout the entire vessel.
resistance arteries; endothelium; conduction
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