OBJECTIVE: Heart and aorta possess biologic clocks, but their involvement in genetic hypertension has been unknown. Plasminogen activator inhibitor-1 (PAI-1) expression is directly regulated by clock genes, while angiotensin II modulates both PAI-1 and clock gene expression. We therefore examined circadian expression of PAI-1 and clock genes, and effects of angiotensin type 1 (AT1) receptor antagonism, in heart and aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. METHODS: We examined cardiac and aortic mRNA expression for PAI-1 and clock genes (Per2, Bmal1, Clock, and Dbp) every 4 h throughout the day by quantitative reverse transcription-polymerase chain reaction, and intervention with the AT1 receptor antagonist candesartan and equihypotensive hydralazine. RESULTS: Cardiac PAI-1 expression was high in the dark, while aortic PAI-1 expression was high in the light. Both cardiac and aortic PAI-1 expression were greater in SHR than in WKY rats. Candesartan treatment decreased cardiac PAI-1 expression only in the dark in WKY rats but throughout the day in SHR. Candesartan but not hydralazine strongly attenuated circadian fluctuation of aortic PAI-1 mRNA in SHR and WKY rats. Clock genes oscillated synchronously in heart and aorta of SHR and WKY rats. Clock gene expression was increased in heart but not aorta of SHR. Candesartan did not affect clock gene expression. CONCLUSIONS: Enhanced expression of clock genes may increase PAI-1 expression in concert with activated renin-angiotensin system in SHR heart. Rather than clock genes, the renin-angiotensin system induces daily fluctuation and increased expression of aortic PAI-1 mRNA in SHR.
OBJECTIVE: Heart and aorta possess biologic clocks, but their involvement in genetic hypertension has been unknown. Plasminogen activator inhibitor-1 (PAI-1) expression is directly regulated by clock genes, while angiotensin II modulates both PAI-1 and clock gene expression. We therefore examined circadian expression of PAI-1 and clock genes, and effects of angiotensin type 1 (AT1) receptor antagonism, in heart and aorta of spontaneously hypertensiverats (SHR) and Wistar-Kyoto (WKY) rats. METHODS: We examined cardiac and aortic mRNA expression for PAI-1 and clock genes (Per2, Bmal1, Clock, and Dbp) every 4 h throughout the day by quantitative reverse transcription-polymerase chain reaction, and intervention with the AT1 receptor antagonist candesartan and equihypotensive hydralazine. RESULTS: Cardiac PAI-1 expression was high in the dark, while aortic PAI-1 expression was high in the light. Both cardiac and aortic PAI-1 expression were greater in SHR than in WKY rats. Candesartan treatment decreased cardiac PAI-1 expression only in the dark in WKY rats but throughout the day in SHR. Candesartan but not hydralazine strongly attenuated circadian fluctuation of aortic PAI-1 mRNA in SHR and WKY rats. Clock genes oscillated synchronously in heart and aorta of SHR and WKY rats. Clock gene expression was increased in heart but not aorta of SHR. Candesartan did not affect clock gene expression. CONCLUSIONS: Enhanced expression of clock genes may increase PAI-1 expression in concert with activated renin-angiotensin system in SHR heart. Rather than clock genes, the renin-angiotensin system induces daily fluctuation and increased expression of aortic PAI-1 mRNA in SHR.
Authors: Peng Y Woon; Pamela J Kaisaki; José Bragança; Marie-Thérèse Bihoreau; Jonathan C Levy; Martin Farrall; Dominique Gauguier Journal: Proc Natl Acad Sci U S A Date: 2007-08-29 Impact factor: 11.205
Authors: Kanika Bagai; James A S Muldowney; Yanna Song; Lily Wang; Jayant Bagai; Kay J Artibee; Douglas E Vaughan; Beth A Malow Journal: Sleep Date: 2014-02-01 Impact factor: 5.849