title: Effects of chronotherapy of benazepril on the diurnal profile of RAAS and clock genes in the kidney of 5/6 nephrectomy rats.
abstract: This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.
authors.affiliation: Department of Nephrology, Wuhan Central Hospital, Wuhan, 430014, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Huang
authors.affiliation: Department of Pathology, Wuhan Central Hospital, Wuhan, 430014, China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, Wuhan Central Hospital, Wuhan, 430014, China.
authors.forename: Xing-Ruo
authors.initials: XR
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Wuhan Central Hospital, Wuhan, 430014, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Peng
authors.affiliation: Department of Science and Education, Wuhan Central Hospital, Wuhan, 430014, China.
authors.forename: Qi-Hui
authors.initials: QH
authors.lastname: Mei
authors.affiliation: Department of Nephrology, Wuhan Central Hospital, Wuhan, 430014, China. whwenli@163.com.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001552:Benzazepines / Q000008:administration & dosage*; D056926:CLOCK Proteins / Q000378:metabolism*; D002940:Circadian Rhythm; D055870:Drug Chronotherapy; D020869:Gene Expression Profiling; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001552:Benzazepines; D056926:CLOCK Proteins; C044946:benazepril