Effects of Chronotherapy of Benazepril on the Diurnal Profile of RAAS and Clock Genes in the Kidney of 5/6 Nephrectomy Rats

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 3; pp. 368 - 374
• Main Author: 黄小妹 袁静萍 曾星若 彭彩霞 梅啓慧 陈文莉
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.06.2013; Department of Nephrology, Wuhan Central Hospital, Wuhan 430014, China%Department of Pathology, Wuhan Central Hospital, Wuhan 430014, China%Department of Science and Education,Wuhan Central Hospital, Wuhan 430014, China
• Subjects: Aldosterone; Animals; Antihypertensive Agents - administration & dosage; Benzazepines - administration & dosage; Circadian Rhythm; CLOCK Proteins - metabolism; Drug Chronotherapy; Gene Expression Profiling; Hypertension, Renal - drug therapy; Hypertension, Renal - physiopathology; Kidney - drug effects; Kidney - physiopathology; Kidney - surgery; Male; Medicine; Medicine & Public Health; mRNA表达; Nephrectomy; Rats; Rats, Wistar; Renin-Angiotensin System - drug effects; Treatment Outcome; Wistar; 上海; 个人资料; 基因表达谱; 大鼠肾脏; 血管紧张素; 钟基因; chronotherapy; circadian; clock genes; benazepril; RAAS; 5/6 subtotal nephrectomy
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1126-7

Summary： 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 ran- domly divided into 4 groups： sham STNx group （control）, STNx group, morning benazepril group （MB） and evening benazepril group （EB）. Benazepril was intragastfically 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）, angio- tensin Ⅱ （Ang Ⅱ ） and aldosterone （Aid） by radioimmunoassay （RIA） and the mRNA expression profile of clock genes （bmall, dbp and per2） by real-time PCR at 12 weeks. Our results showed that no signifi- cant 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 Aid and RA content of a day between the MB group and EB group. The expression peak of bmall 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.