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Key role of Pannexin‐based hemichannels in flow‐induced nitric oxide production in resistance arteries
Author(s) -
Perez Francisco R,
Gaete Pablo,
Boric Mauricio,
Figueroa Xavier
Publication year - 2012
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.26.1_supplement.853.9
Subject(s) - pannexin , ppads , enos , chemistry , nitric oxide , purinergic receptor , microbiology and biotechnology , pharmacology , nitric oxide synthase , connexin , medicine , receptor , endocrinology , biology , biochemistry , gap junction , intracellular
Nitric oxide (NO) production and connexin‐based channels play a key role in the control and coordination of vascular function. Blood flow induces NO production by the activation of endothelial NO synthase phosphorylation at serine 1177 (P‐eNOS S1177 ) through the PI3K/Akt pathway. The participation of connexin‐ or pannexin‐formed hemichannels in the response to flow has not been evaluated. We used the rat arterial mesenteric bed to study the involvement of hemichannels in flow‐induced NO production. Mesenteric vessels were stimulated with flow by increasing the perfusion rate from 2 to 10 mL/min and hemichannel activity was assessed by ethidium or Lucifer Yellow uptake. Flow increased NO production, Akt‐dependent P‐eNOS S1177 , ATP release and endothelial hemichannel activity. Treatment with 18‐beta‐glycyrrhetinic acid or probenecid, but not La 3+ , blocked the hemichannel activation and Akt dependent‐P‐eNOS S1177 induced by flow. The increase in P‐eNOS S1177 was prevented by the specific inhibition of P2Y1 receptors with MRS2179 or global inhibition of purinergic receptors with PPADS, but not by the P2X receptor blocker iso‐PPADS. These results suggest that pannexin hemichannel‐mediated ATP release is involved in the activation of NO production in response to flow, which may be involved in the development of cardiovascular diseases. FONDECYT 1100850, 1090757, 1111033, Anillos ACT‐71.