Rationale: Macrophages change their phenotype and biological functions depending on the microenvironment. In atherosclerosis, oxidative tissue damage accompanies chronic inflammation; however, macrophage phenotypic changes in response to oxidatively modified molecules are not known.Objective: To examine macrophage phenotypic changes in response to oxidized phospholipids that are present in atherosclerotic lesions. Methods and Results:

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Rationale The coordination of vascular smooth muscle cell (VSMC) constriction plays an important role in vascular function such as regulation of blood pressure. However, the mechanism responsible for VSMC communication is not clear in the resistance vasculature. Pannexins (Panx) are purine releasing channels permeable to the vasoconstrictor ATP and thus may play a role in the coordination of VSMC constriction. Objective We investigated the role of pannexins in phenylephrine (PE) and KCl mediated constriction of resistance arteries. Methods and Results Western blot, immunohistochemistry and immunogold labeling coupled to scanning and transmission electron microscopy revealed the presence of Panx1 but not Panx2 or Panx3 in thoracodorsal resistance arteries (TDA). Functionally, the contractile response of pressurized TDA to PE was significantly decreased by multiple Panx inhibitors (mefloquine, probenecid and 10Panx1), ectonucleotidase (apyrase) and purinergic receptor inhibitors (suramin and reactive-blue-2). Electroporation of TDA with either Panx1-GFP or Panx1 siRNA showed enhanced and decreased constriction respectively in response to PE. Lastly, the Panx inhibitors did not alter constriction in response to KCl. This result is consistent with co-immunoprecipitation experiments from TDA, which suggested an association between Panx1 and α1D-adrenoreceptor. Conclusions Our data demonstrate for the first time a key role for Panx1 in resistance arteries, by contributing to the coordination of VSMC constriction and possibly regulation of blood pressure.