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Evidence for Endothelin Regulation of Bmal1 Expression In The Renal Vasculature
Author(s) -
Chen Daian,
Speed Joshua S,
Hyndman Kelly A,
Kasztan Malgorzata,
Johnston Jermaine J,
Inscho Edward W,
Young Martin E,
Pollock David M,
Pollock Jennifer S
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.964.12
Subject(s) - endocrinology , circadian rhythm , medicine , zeitgeber , clock , period (music) , blood pressure , kidney , endothelin 1 , circadian clock , biology , endothelin receptor , knockout mouse , endothelins , receptor , acoustics , physics
The circadian system is responsible for regulating a wide variety of physiological rhythms. Bmal1 (also known as Arntl) is a central element of the core clock genes. Bmal1 is ubiquitously expressed, however Bmal1 functions in a tissue‐specific manner. Bmal1 knockout mice display a loss of circadian blood pressure rhythm and aortic dysfunction. Endothelin (ET‐1) is a potent vasoconstrictor especially in the renal vasculature. Recently, we reported that high salt diet leads to renal vascular dysfunction through activation of the ET‐1 system. However, very little is known about the role of clock genes in the renal vasculature under varying salt diets. We hypothesized that high salt diet via the ET‐1 system uncouples the oscillating expression of Bmal1 in the renal vasculature. We utilized adult male rats (12 weeks old) deficient in the ET B receptor (ET B Def) and transgenic controls (Tg) fed a normal salt diet (0.4% NaCl) or high salt diet (4% NaCl). Under high salt conditions, ET B Def rats display high circulating ET‐1 levels as well as an exaggerated circadian blood pressure rhythm. Renal vessels were isolated from ET B Def and Tg controls every four hours during the inactive (light) period at Zeitgeber time (ZT) 0, 4, 8, and the active (dark) period at ZT12, 16, and 20 for the 24 hr period, and qRT‐PCR was conducted for Bmal1 mRNA. Bmal1 expression displays a rhythmic pattern showing peak expression at ZT0 in both Tg control and ET B Def rats on a normal salt diet. Bmal1 mRNA expression is attenuated in the renal vasculature of ET B Def rats compared to Tg controls (Tg control: ZT0 5755±1326, ZT4 4090±408, ZT8 923±237, ZT12 758±366, ZT16 732±181, ZT20 3339±1347 copy number/ng RNA; ET B Def: ZT0 2938±497, ZT4 2147±562, ZT8 647±349, ZT12 92±7, ZT16 387±17, ZT20 2148±406 copy number/ng RNA). High salt diet did not alter the magnitude or circadian oscillation of Bmal1 mRNA expression in Tg control rats. However, high salt diet in ET B Def rats significantly increased Bmal1 mRNA expression compared to ET B Def rats on normal salt. These data suggest that in the renal vasculature a functionally intact ET‐1 system is required in the renal vasculature to exhibit a normal circadian Bmal1 expression. Further analyses are required for understanding the interrelationship of the ET‐1 system and circadian regulation of renal vascular function. Support or Funding Information AHA Strategically Focused Hypertension Research Network Grant