دورية أكاديمية
Knockout of the Circadian Clock Protein PER1 (Period1) Exacerbates Hypertension and Increases Kidney Injury in Dahl Salt-Sensitive Rats.
العنوان: | Knockout of the Circadian Clock Protein PER1 (Period1) Exacerbates Hypertension and Increases Kidney Injury in Dahl Salt-Sensitive Rats. |
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المؤلفون: | Zietara A; Department of Molecular Pharmacology and Physiology (A.Z., V.L., L.V.D., C.A.K., A.S.), University of South Florida, Tampa.; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.Z., D.R.S., A.M.G.), University of Florida., Spires DR; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.Z., D.R.S., A.M.G.), University of Florida., Juffre A; Department of Biochemistry and Molecular Biology (A.J., L.G.D., M.L.G.), University of Florida.; Department of Physiology and Aging (A.J., H.M.C., G.R.C., M.L.G.), University of Florida., Costello HM; Department of Physiology and Aging (A.J., H.M.C., G.R.C., M.L.G.), University of Florida., Crislip GR; Department of Physiology and Aging (A.J., H.M.C., G.R.C., M.L.G.), University of Florida., Douma LG; Department of Biochemistry and Molecular Biology (A.J., L.G.D., M.L.G.), University of Florida., Levchenko V; Department of Molecular Pharmacology and Physiology (A.Z., V.L., L.V.D., C.A.K., A.S.), University of South Florida, Tampa., Dissanayake LV; Department of Molecular Pharmacology and Physiology (A.Z., V.L., L.V.D., C.A.K., A.S.), University of South Florida, Tampa., Klemens CA; Department of Molecular Pharmacology and Physiology (A.Z., V.L., L.V.D., C.A.K., A.S.), University of South Florida, Tampa.; Hypertension and Kidney Research Center (C.A.K., A.S.), University of South Florida, Tampa., Nikolaienko O; Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kyiv, Ukraine (O.N.)., Geurts AM; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.Z., D.R.S., A.M.G.), University of Florida., Gumz ML; Department of Biochemistry and Molecular Biology (A.J., L.G.D., M.L.G.), University of Florida.; Department of Physiology and Aging (A.J., H.M.C., G.R.C., M.L.G.), University of Florida.; Division of Nephrology, Department of Medicine, Hypertension, and Renal Transplantation (M.L.G.), University of Florida.; Center for Integrative Cardiovascular and Metabolic Disease, Gainesville (M.L.G.)., Staruschenko A; Department of Molecular Pharmacology and Physiology (A.Z., V.L., L.V.D., C.A.K., A.S.), University of South Florida, Tampa.; Hypertension and Kidney Research Center (C.A.K., A.S.), University of South Florida, Tampa.; James A. Haley Veterans' Hospital, Tampa, FL (A.S.). |
المصدر: | Hypertension (Dallas, Tex. : 1979) [Hypertension] 2022 Nov; Vol. 79 (11), pp. 2519-2529. Date of Electronic Publication: 2022 Sep 12. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]- |
مواضيع طبية MeSH: | Circadian Clocks*/genetics , Hypertension*/genetics , Hypertension*/metabolism , Kidney Diseases*, Animals ; Male ; Rats ; Blood Pressure/physiology ; Kidney/metabolism ; Mice, Knockout ; Period Circadian Proteins/genetics ; Period Circadian Proteins/metabolism ; Rats, Inbred Dahl ; Sodium/metabolism ; Sodium Chloride/metabolism ; Sodium Chloride, Dietary/pharmacology ; Transcription Factors/metabolism ; Mice |
مستخلص: | Background: Circadian rhythms play an essential role in physiological function. The molecular clock that underlies circadian physiological function consists of a core group of transcription factors, including the protein PER1 (Period1). Studies in mice show that PER1 plays a role in the regulation of blood pressure and renal sodium handling; however, the results are dependent on the strain being studied. Using male Dahl salt-sensitive (SS) rats with global knockout of PER1 (SS Per1-/- ), we aim to test the hypothesis that PER1 plays a key role in the regulation of salt-sensitive blood pressure. Methods: The model was generated using CRISPR/Cas9 and was characterized using radiotelemetry and measures of renal function and circadian rhythm. Results: SS Per1-/- rats had similar mean arterial pressure when fed a normal 0.4% NaCl diet but developed augmented hypertension after three weeks on a high-salt (4% NaCl) diet. Despite being maintained on a normal 12:12 light:dark cycle, SS Per1-/- rats exhibited desynchrony mean arterial pressure rhythms on a high-salt diet, as evidenced by increased variability in the time of peak mean arterial pressure. SS Per1-/- rats excrete less sodium after three weeks on the high-salt diet. Furthermore, SS Per1-/- rats exhibited decreased creatinine clearance, a measurement of renal function, as well as increased signs of kidney tissue damage. SS Per1-/- rats also exhibited higher plasma aldosterone levels. Conclusions: Altogether, our findings demonstrate that loss of PER1 in Dahl SS rats causes an array of deleterious effects, including exacerbation of the development of salt-sensitive hypertension and renal damage. |
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معلومات مُعتمدة: | R01 DK109570 United States DK NIDDK NIH HHS; I01 BX004024 United States BX BLRD VA; R24 HL114474 United States HL NHLBI NIH HHS; R56 DK128271 United States DK NIDDK NIH HHS; R35 HL135749 United States HL NHLBI NIH HHS |
فهرسة مساهمة: | Keywords: aldosterone; arterial pressure; circadian rhythm; mice; sodium |
المشرفين على المادة: | 0 (Per1 protein, mouse) 0 (Per1 protein, rat) 0 (Period Circadian Proteins) 9NEZ333N27 (Sodium) 451W47IQ8X (Sodium Chloride) 0 (Sodium Chloride, Dietary) 0 (Transcription Factors) |
تواريخ الأحداث: | Date Created: 20220912 Date Completed: 20221122 Latest Revision: 20240226 |
رمز التحديث: | 20240226 |
مُعرف محوري في PubMed: | PMC9669134 |
DOI: | 10.1161/HYPERTENSIONAHA.122.19316 |
PMID: | 36093781 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1524-4563 |
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DOI: | 10.1161/HYPERTENSIONAHA.122.19316 |