Abstract P124: Nlrp3 Activation by Endothelin-1 Mediates Neutrophil Recruitment in Cavernosal Tissue of DOCA/salt Mice

Abstract

Introduction: Endothelin-1 (ET-1) induces penile detumescence and acts as an important mediator of chronic inflammation. NACHT, leucine reach repeat (LRR) and PYD domain-containing protein 3 (NLRP3) releases the active form of IL-1β. This cytokine is involved in neutrophil recruitment from the circulation to the tissues. Increasing evidence shows that neutrophil infiltration is involved in the genesis and aggravation of various cardiovascular diseases. Hypothesis: NLRP3 activation by ET-1 mediates neutrophil infiltration in the corpora cavernosa (CC) of DOCA/salt hypertensive mice. Methods: All protocols were approved by the Animals Use Ethics Committee (CEUA 213/2016). Male C57BL/6 (WT) and NLRP3 deficient mice (NLRP3 -/- ) were either induced to DOCA/salt hypertension or SHAM and treated with bosentan or vehicle. Caspase-1 and IL-1β activities were determined in CC. NF-κB, ICAM-1 and VCAM-1 expressions in CC were determined by immunohistochemistry. Flow cytometry was performed to evaluate the infiltration of myeloid cells into CC. Results: DOCA/salt hypertension increased caspase-1 and IL-1β activities in CC. NF-κB, ICAM-1, VCAM-1 and neutrophil infiltration were increased in CC of DOCA/salt mice. The treatment with bosentan or the absence of NLRP3 prevented all these alterations in DOCA/salt mice. Conclusion: ET-1-induced NLRP3 activation is involved in neutrophil recruitment in CC of DOCA/salt hypertensive mice.