title: Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.
abstract: High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na(+) channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Hexuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Zongshi
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine of Zunyi Medical College, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology and Physiology, 6341-B Medical Biomolecular Research Building, CB #7545, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Arendshorst
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine of Zunyi Medical College, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, China.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Shang
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006973:Hypertension / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020303:Rats, Inbred Dahl; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013564:Sympathetic Nervous System / Q000098:blood supply / Q000187:drug effects
chemical_list: D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary; D002110:Caffeine; D012964:Sodium; D000263:Adenylate Kinase