title: Desoxycorticosterone pivalate-salt treatment leads to non-dipping hypertension in Per1 knockout mice.
abstract: Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1-mediated blood pressure regulation in a salt-resistant, normotensive mouse model, C57BL/6J.
  
  
  
  Blood pressure was measured using radiotelemetry. After control diet, wild-type (WT) and Per1 (KO) knockout mice were given a high salt diet (4% NaCl) and the long-acting mineralocorticoid deoxycorticosterone pivalate. Blood pressure and activity rhythms were analysed to evaluate changes over time.
  
  
  
  Blood pressure in WT mice was not affected by a high salt diet plus mineralocorticoid. In contrast, Per1 KO mice exhibited significantly increased mean arterial pressure (MAP) in response to a high salt diet plus mineralocorticoid. The inactive/active phase ratio of MAP in WT mice was unchanged by high salt plus mineralocorticoid treatment. Importantly, this treatment caused Per1 KO mice to lose the expected decrease or 'dip' in blood pressure during the inactive compared to the active phase.
  
  
  
  Loss of PER1 increased sensitivity to the high salt plus mineralocorticoid treatment. It also resulted in a non-dipper phenotype in this model of salt-sensitive hypertension and provides a unique model of non-dipping. Together, these data support an important role for the circadian clock protein PER1 in the modulation of blood pressure in a high salt/mineralocorticoid model of hypertension.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.|Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Solocinski
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Holzworth
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: K-Y
authors.initials: KY
authors.lastname: Cheng
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.|North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Lynch
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Cain
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.|North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Wingo
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.|Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.|North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Gumz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008901:Mineralocorticoids / Q000494:pharmacology; D056950:Period Circadian Proteins / Q000172:deficiency / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
chemical_list: D008901:Mineralocorticoids; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D017673:Sodium Chloride, Dietary; C019323:deoxycortone pivalate; D003900:Desoxycorticosterone
keywords: blood pressure; circadian rhythm; salt sensitivity; telemetry