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Leptin‐Mediated Increases in Sympathetic Tone Decreases Alpha(1D)‐Adrenergic Receptor Expression in Arteries and Adrenals
Author(s) -
Newell Maegan,
Momtahan Mina,
Kennard Simone,
Belin de Chantemele Eric J.
Publication year - 2016
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.30.1_supplement.964.15
Subject(s) - medicine , endocrinology , leptin , receptor , mesenteric arteries , adrenergic receptor , blood pressure , vasoconstriction , aorta , sympathetic nervous system , vascular smooth muscle , chemistry , obesity , artery , smooth muscle
Obesity is a major risk factor for hypertension with adipocyte‐derived leptin causing sympathoactivation. Deletion of protein tyrosine phosphatase 1B (PTP1B) is known to increase leptin sensitivity, making it an ideal model for studying the cardiovascular effects of leptin separate from obesity. Our lab has previously characterized the reduction of a 1D ‐adrenergic receptor expression and reactivity in the aorta that accompanies leptin‐mediated increases in vascular sympathetic tone. Directly implicated in sympathetic regulation of blood pressure through vasoconstriction, the decreased expression and reactivity of the α 1D receptor is suggestive of adrenergic desensitization as a protective mechanism against the development of hypertension. This study tested the hypothesis that, in addition to the aorta, leptin‐induced, sympatho‐mediated decreased adrenergic receptor expression occurs in vascular beds and most prominently in those associated with blood pressure regulation as well as in the norepinephrine‐and epinephrine‐releasing adrenals. Real‐time PCR conducted on tissues collected from wild‐type (WT) and PTP1B knockout animals (KO) revealed that leptin‐mediated increases in sympathetic tone decreased α 1D ‐receptor expression in aorta (WT: 1.08±0.15 vs. KO: 0.84±0.15), adrenals (WT: 1.08±0.12 vs. KO: 0.67±0.10), and renal (WT: 1.08±0.11 vs. KO: 0.87±0.11) and mesenteric arteries (WT: 1.15±0.24 vs. KO: 0.71±0.12). Additionally, this study investigated the distribution of α 1D receptors among tissues and found tenfold and thirtyfold increased α 1D receptor expression in the adrenals and renal arteries, respectively, and no statistical difference of the expression levels in the mesenteric arteries as compared to the aorta. These data support the hypothesis that leptin‐mediated sympatho‐activation decreases adrenergic receptor expression and highlights the adrenals and renal arteries as potential pathway targets for leptin‐induced sympathoactivation.