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Sex‐Dependent Regulation of Blood Pressure by the Circadian Clock Protein Per1
Author(s) -
Solocinski Kristen,
Cheng KitYan,
Lynch I. Jeanette,
Cain Brian D.,
Wingo Charles S.,
Gumz Michelle L.
Publication year - 2017
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.31.1_supplement.1026.18
Subject(s) - per1 , endocrinology , circadian rhythm , medicine , blood pressure , knockout mouse , mineralocorticoid , biology , wild type , circadian clock , clock , aldosterone , genetics , gene , receptor , mutant
The circadian clock is integral to the maintenance of daily rhythms of many physiological outputs including blood pressure. Our lab has demonstrated the importance of the clock protein Per1 to blood pressure regulation. Previously, we determined the effects of a high salt diet plus mineralocorticoid on Per1‐mediated blood pressure regulation in male C57BL/6 mice (Solocinski et al. Acta Physiol 2016). As expected, mean arterial pressure (MAP) in wild type mice was not affected by a high salt diet (4%)(HS) plus injection with the long‐acting mineralocorticoid deoxycorticosterone pivalate (DOCP). However, Per1 knockout mice exhibited non‐dipping hypertension in response to this treatment. The goal of the present study was to determine the role of Per1 in the regulation of MAP in female mice. For the first time, we demonstrate that loss of a circadian clock protein in female mice results in increased MAP relative to littermate wild type control mice on a C57BL/6 background. These mice were subjected to HS/DOCP treatment as well. In contrast to what we previously observed in male wild type mice, female wild type mice did experience a significant increase in MAP in response to HS/DOCP (7.35 ± 1.00 mmHg p < 0.0001). The Per1 knockout female mice also experienced an increase (8.29 ± 1.17 mmHg, p < 0.0001). Neither genotype experienced changes in the day/night MAP ratio in response to HS/DOCP. Together these data demonstrate that Per1 is important for MAP regulation in female animals and that this regulation appears to be salt‐ and mineralocorticoid‐independent. This effect is distinct from the non‐dipping hypertension seen in male Per1 knockout mice, demonstrating that female sex appears to be protective against Per1‐ mediated non‐dipping hypertension in response to HS/DOCP. Together these data support an important role for the circadian clock protein Per1 in the modulation of blood pressure and suggest that Per1 acts in a sex‐dependent manner in the regulation of cardiovascular rhythms. Support or Funding Information NIH NIDDK UF Department of Medicine, Division of Nephrology American Society of Nephrology UF Hypertension CenterT32 Grant # 2T32HL083810 American Heart Association