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Voltage‐dependent Na + channels are essential for the propagation of electrically induced vasodilation by the endothelium.
Author(s) -
Figueroa Xavier F,
Day Kathleen H,
Damon David N,
Ramos Susan,
Duling Brian R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a277-a
Subject(s) - vasodilation , arteriole , chemistry , tetrodotoxin , stimulation , endothelium , biophysics , constriction , vasoconstriction , medicine , microcirculation , anesthesia , pharmacology , biology
Focal electrical stimulation of arterioles activates a vasoconstriction restricted to the stimulation site and a non‐decremental conducted dilation. We used the mouse cremaster preparation to analyze the mechanisms involved in the propagation of electrically induced dilation. Arterioles were stimulated at 30Hz, 2ms, 30V for 10s and changes in diameter were assessed at the stimulation site (local) and at 500, 1000 and 2000μm upstream. The endothelial damage produced by the injection of an air bubble via a side‐branch of the stimulated arteriole blocked the conduction of the dilation without affecting the local response. A similar result was observed with the local anesthetic, bupivacaine (500μM), which is a lipid‐soluble voltage‐dependent Na + channel (Na v ) blocker. Expression of the Na v isoforms Na v 1.2, Na v 1.6 and Na v 1.9 was detected in the endothelial cells of cremasteric arterioles by immunocytochemistry. However, the water‐soluble Na v blocker, tetrodotoxin (1μM), attenuated but did not block the propagation of the electrically induced dilation, suggesting that access to endothelial Na v is restricted for hydrophilic drugs. Consistent with this idea, the lipid‐soluble activator of Na v , veratridine (100μM), induced an endothelium‐ dependent dilation and the water‐soluble activators, α‐pompilidotoxin (α‐PMTX, 30M) and ATX‐II (10μM), evoked constriction. These results indicate that the electrically induced vasodilator signal is propagated through the endothelium by the regenerative activation of Na v . Grants: NIH #HL53318, AHA #0325730U.