Neflamapimod induces vasodilation in resistance mesenteric arteries by inhibiting p38 MAPKα and downstream Hsp27 phosphorylation.

ABSTRACT: Neflamapimod, a selective inhibitor of p38 mitogen activated protein kinase alpha (MAPKα), is under clinical investigation for its efficacy in Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB). Here, we investigated if neflamapimod-mediated acute inhibition of p38 MAPKα could induce vasodilation in resistance-size rat mesenteric arteries. Our pressure myography data demonstrated that neflamapimod produced a dose-dependent vasodilation in mesenteric arteries. Our Western blotting data revealed that acute neflamapimod treatment significantly reduced the phosphorylation of p38 MAPKα and its downstream target heat-shock protein 27 (Hsp27) involved in cytoskeletal reorganization and smooth muscle contraction. Likewise, non-selective inhibition of p38 MAPK by SB203580 attenuated p38 M

SUBMITTER: Pandey AK 

PROVIDER: S-EPMC8941071 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature