title: Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome.
abstract: Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration, and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension.
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Surgery, Third Affiliated Hospital of Peking University, Beijing 100871, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Haibao
authors.initials: H
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Fanxin
authors.initials: F
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Chuanyun
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Peking-Tsinghua Center for Life Sciences, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.|Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D000077545:Eplerenone; D017127:Glycation End Products, Advanced / Q000097:blood*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008253:Macaca mulatta; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D023421:Models, Animal; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013686:Telemetry; D014851:Wakefulness
chemical_list: D000959:Antihypertensive Agents; D017127:Glycation End Products, Advanced; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone