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Leptin improves vascular function by increasing NO formation by an eNOS‐independent pathway
Author(s) -
Schröder Katrin,
Benkhoff Sebastian B.,
Brandes Ralf P.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.643.11
Subject(s) - enos , leptin , medicine , endocrinology , function (biology) , chemistry , cardiology , microbiology and biotechnology , biology , obesity , nitric oxide , nitric oxide synthase
Nitric oxide (NO) plays central role in regulating vascular tone. Three types of NO synthase exist in mammalian cells: the calcium‐dependent endothelial NOS (eNOS) and neuronal NOS (nNOS) isoforms and the constitutively‐active inducible NOS (iNOS). Leptin is an adipose tissue‐derived peptide hormone which increases angiogensis but with poorly defined vascular functions, which were studied here. Wild type (WT) and eNOS−/− mice were treated with or without leptin (0.5 mg/kg/day by mini pump) for 14 days. Isolated vessel recordings revealed that leptin‐treatment resulted in an acetylcholine (ACh)‐induced relaxation in rings from eNOS−/− mice which was otherwise absent. Blocking total NOS activity by nitro‐L‐arginine (L‐ NA) abolished reactivity to ACh in all groups, whereas a selective nNOS inhibitor blocked responses only in rings from eNOS−/− treated with leptin. Basal NO formation estimated from acute L‐NA‐induced contraction was absent in native rings of eNOS−/− mice but detectable after treatment with leptin. Similar results were obtained using nNOS inhibitors. In HUVECs, leptin increased JAK2 and STAT3 phosphorylation, signals which are known to regulate nNOS expression. Quantitative PCR of isolated vessels revealed that nNOS expression was increased by infusion of leptin. We conclude that leptin increases the vascular production of NO and improves ACh‐induced relaxation by the induction of nNOS.