Changes in contractile protein gene expression with ageing and with captopril-induced regression of hypertrophy in the spontaneously hypertensive rats

Background Left ventricular hypertrophy (LVH) is present in young spontaneo usly hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats and treatment of SHR with captopril leads to regression of LVH. Hypert rophy produces changes in gene expression for myofibrillar proteins with in creased ratios of skeletal to cardiac actin and beta to alpha-myosin heavy chain (MHC). Objectives The objective of this study was to follow changes in transcript prevalence for these four proteins during ageing and with captopril treatme nt in SHR and WKY rats. Methods Untreated SHR and WKY rats were studied at 100, 156, 350 and 450 da ys, Groups at 100 and 350 days were divided into a treatment group (given c aptopril) and untreated controls. Transcripts were measured using in situ h ybridization. Results Both cardiac and skeletal actin were increased in untreated SHR com pared to WKY rats (P < 0.01 and P < 0.05, respectively), alpha-MHC was incr eased (P < 0.01) whilst beta-MHC was normal in 100-day-old SHR (an age when LVH was present) compared with WKY rats. With ageing, alpha-MHC declined a nd beta-MHC increased giving the increased ratio of beta to alpha-MHC trans cripts reported by other investigators. Treatment of SHR led to a significa nt decline in skeletal actin transcripts (P < 0.01) and reversed the rise i n beta-MHC expression that occurred with ageing (P < 0.01), Conclusions LVH in SHR is associated with increased skeletal and cardiac ac tin transcripts, Despite unequivocal LVH in SHR at 100 days of age, a rathe r than beta-MHC transcripts were increased, Only with ageing did the classi cally reported increased ratio of beta to alpha-MHC transcripts become appa rent Captopril treatment reduced skeletal actin transcripts and reversed th e increase in beta-MHC that occurred with ageing. J Hypertens 2000, 18:1297 -1306 (C) Lippincott Williams & Wilkins.