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Vasoactive effects of endothelin‐1 in the mesentery and cremaster muscle of leptin deficient mice (674.11)
Author(s) -
Vigilance Jacqueline,
Frame Mary
Publication year - 2014
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.28.1_supplement.674.11
Subject(s) - cremaster muscle , endocrinology , medicine , vasodilation , arteriole , intravital microscopy , vasoconstriction , microcirculation , endothelin 1 , endothelin receptor , leptin , mesentery , chemistry , anatomy , receptor , obesity
Leptin has been shown to up‐regulate endothelin‐1 production. We investigated the responses to endothelin‐1 (ET) in leptin deficient diabetic mice (db/db) in comparison to C57BL/6J (C57) genetic background mice in the absence or presence of endogenous NO (LNNA), and with blockade of the ETB receptor (PD142893, BQ788). The cremaster muscle of anesthetized (50 mg/kg Nembutal or 4% isoflurane) mice (n=33) was prepared for intravital microscopy. Arteriole(A)/venule(V) pairs were chosen for study. Baseline diameters in the cremaster (A/V, 30/35 um) were ~20‐30% larger than in db/dbs; in the mesentery (60/120 um) they were similar for the 2 strains. Vasodilatory tone (adenosine, 10‐4M) was not significantly different between strains, and was lower in mesentery vs. cremaster. Vasoconstrictor tone (Phenylephrine, 10‐4M) was decreased in db/db compared to C57 in the cremaster, but not mesentery. ET1 dose dependent constriction in the C57 or db/db cremaster (logM EC50: C57 ‐11.9±29.6 A, ‐11.7±2.8 V; db/db ‐11.7±4.4 A, ‐10.0 V) was suppressed by LNNA, and enhanced with ETB antagonism to a greater extent in the A vs. V. In the mesentery, baseline constriction to ET1 was diminished to a greater extent in the db/db vs C57 and was suppressed by LNNA and enhanced with ETB antagonism. Thus, the leptin deficient mouse exhibits a tissue specific loss of ET1 mediated constriction. Yet, the potential role for ETB mediated vasodilation appears similar for C57 and db/db in both tissues Grant Funding Source : NIH DK68401, The UWI