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Vascular smooth muscle cells limit endothelial control of vasoreactivity via ROS production through myoendothelial communications
Author(s) -
Billaud Marie,
Marthan Roger,
Savineau JeanPierre,
Guibert Christelle
Publication year - 2009
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.23.1_supplement.627.3
Subject(s) - gap junction , connexin , carbenoxolone , pannexin , vascular smooth muscle , chemistry , calcium , serotonin , endothelium , western blot , microbiology and biotechnology , biology , biophysics , biochemistry , endocrinology , smooth muscle , intracellular , receptor , organic chemistry , gene
Although cross‐talk between endothelial (EC) and smooth muscle cells (SMC) through myoendothelial gap junctions play a major role in the vasoreactivity, the transduction pathways remain unclear. Here we tested the hypothesis of the role of ROS and gap junctions in this cross‐talk. Connexin (Cx)‐ mimetic peptide targeted against Cx 37 and Cx 43 ( 37,43 Gap27) reduced (1) the contractile and calcium responses to serotonin (5‐HT) simultaneously recorded in small intrapulmonary arteries and (2) abolished the diffusion, in the SMC, of carboxyfluorescein‐AM loaded in EC. Quantitative RT‐PCR, Western Blot analyses and immunofluorescent labeling showed the presence of Cx 37, 40 and 43. Superoxyde dismutase and catalase which destroy superoxyde anion and H 2 O 2 respectively also decreased the contractile and calcium responses to 5‐HT. Both Cx‐ and ROS‐mediated effects on the responses to 5‐HT were reversed by L‐NAME and/or endothelium removal thus reflecting a cross‐talk between SMC and EC through ROS and gap junctions. Electronic paramagnetic resonance demonstrated that superoxyde anion production by 5‐HT originated from the SMC only. Moreover, 5‐HT decreased cyclic GMP content in isolated arteries. These data support a model where superoxyde anion produced by 5‐HT in the SMC will pass through myoendothelial gap junctions to reduce endothelial NO‐dependent control of vasoreactivity.