Sensory nerve‐dependent prolonged opening of pannexin‐1‐based channels controls eNOS phosphorylation in mesenteric arteries

Abstract

In this work, we analyzed if perivascular sensory nerves (PSN) or pannexin 1 (Panx1)‐based channels control eNOS activity in resistance arteries. PSN of isolated arterial mesenteric bed of rat were activated with capsaicin (1 μM, 20 min) and acetylcholine (ACh)‐induced vasodilation and NO production were assessed 1 h later. Panx1‐based channel activity was evaluated by ethidium uptake and eNOS phosphorylation (p‐eNOS) by Western blot. Ethidium uptake was undetectable in control conditions, but stimulation with capsaicin or calcitonin gene‐related peptide (CGRP) induced robust dye uptake for more than 1 h. ACh‐induced NO‐dependent vasodilation and NO production, decreased drastically 1 h after capsaicin treatment, which was associated with a reduction in p‐eNOSSer1177 but not in p‐eNOSTh495. CGRP8–37 (CGRP receptor blocker) and probenecid (Panx1‐based channel blocker) inhibited both CGRP‐ and capsaicin‐activated ethidium uptake. These blockers also prevented the reduction in p‐eNOSSer1177 and NO‐dependent dilation. Consistent with this, Panx1‐based channel blockade with 10Panx prevented the inhibition in NO production observed after capsaicin treatment. These results suggest that capsaicin‐sensitive sensory nerves activation induces a prolonged opening of Panx1‐based channels, which leads to a reduction of phosphorylation‐mediated eNOS activity.FONDECYT 1100850, Anillos ACT‐71, AT2012