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Deletion of Protein Tyrosine Phosphatase 1b (Ptp1b) in Proopiomelanocortin (POMC) Neurons Reduces Sympathetic Tone and Protects Mice from Leptin‐Induced High Blood Pressure
Author(s) -
BruderNascimento Thiago,
Benjamin Butler,
Bence Kendra,
Belin de Chantemelle Eric
Publication year - 2015
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.29.1_supplement.984.18
Subject(s) - medicine , endocrinology , phenylephrine , leptin , proopiomelanocortin , blood pressure , adrenergic , receptor , chemistry , biology , obesity
Ptp1b is a negative regulator of leptin signaling. Deletion of Ptp1b in POMC neurons increases energy expenditure and protects mice from obesity and type 2 diabetes. However, whether POMC‐Ptp1b deletion sensitizes the cardiovascular system to leptin is unknown. We addressed this question by analyzing the cardiovascular phenotype of flox/flox (WT) and POMC‐Ptp1b KO mice (KO), at baseline and after 7 days of chronic leptin infusion. Conscious blood pressure (BP) and heart rate recordings revealed that POMC‐Ptp1b deletion did not affect baseline BP [WT: 118.3±4.1 vs KO: 117.9± 4.2 mmHg]. However KO mice exhibit a lower BP response to ganglionic blockade [WT: ‐30±4 vs KO: ‐15±6 % drop, P<0.05] that suggests a decreased neurogenic control of BP. Reduced sympathetic tone was further confirmed by showing that KO mice exhibit low plasma catecholamine levels [WT: 3765±483 vs KO: 2113±521 pg/mL, P<0.05, HPLC] compared to WT mice and a compensatory increase in vascular adrenergic tone (increased vascular constriction to phenylephrine) and a 1 adrenergic receptors expression (qRT‐PCR). Furthermore chronic sympatho‐activation for 7 days via phenylephrine infusion restored vascular adrenergic tone in KO mice. POMC‐Ptp1b deletion abolished leptin‐induced increase in BP [WT: +13±2.5 mmHg, P<0.05 vs baseline; KO: +4±1.9 mmHg, NS]. However chronic leptin infusion restored vascular adrenergic tone in POMC‐Ptp1b KO mice by increasing vascular sympathoactivation. These data suggests that deletion of Ptp1b in POMC neurons protects from leptin‐induced high BP by reducing neurogenic control of blood pressure.