TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway

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Background and aimsTransient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. MethodsHuman umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca2+-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation. NO metabolites, protein expression, and inflammatory molecules were evaluated by Griess assay and immune assay-based multiplex analysis, respectively. Monocyte adhesion was determined by measuring the fluorescently labeled human monocytes attached to LPS-stimulated ECs. ResultsIn HUVECs, treatment with CAP increased NO production, and CAP-induced NO production was accompanied by increased eNOSser1177 phosphorylation. Additionally, CAP attenuated LPS-induced cytokine and chemokine production, adhesion molecule expression, activation of NF-κB, and monocyte adhesion in HUVECs, and these effects were abrogated by the inhibition of TRPV1, NOS, or Ca2+-dependent PI3K/Akt pathway. Moreover, these protective actions of TRPV1 were also observed in renal MVECs isolated from DOCA-salt hypertensive mice. ConclusionsOur results indicate that TRPV1 activation suppresses the inflammatory response of ECs via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway, the protective effects are also documented in ECs derived from salt-sensitive hypertensive mice.