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 spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats and treatment of SHR with captopril leads to regression of LVH. Hypertrophy produces changes in gene expression for myofibrillar proteins with increased 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 treatment in SHR and WKY rats.

METHODS

Untreated SHR and WKY rats were studied at 100, 156, 350 and 450 days. Groups at 100 and 350 days were divided into a treatment group (given captopril) and untreated controls. Transcripts were measured using in situ hybridization.

RESULTS

Both cardiac and skeletal actin were increased in untreated SHR compared to WKY rats (P<0.01 and P<0.05, respectively). alpha-MHC was increased (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 and beta-MHC increased giving the increased ratio of beta to alpha-MHC transcripts reported by other investigators. Treatment of SHR led to a significant decline in skeletal actin transcripts (P< 0.01) and reversed the rise in beta-MHC expression that occurred with ageing (P< 0.01).

CONCLUSIONS

LVH in SHR is associated with increased skeletal and cardiac actin transcripts. Despite unequivocal LVH in SHR at 100 days of age, alpha rather than beta-MHC transcripts were increased. Only with ageing did the classically reported increased ratio of beta to alpha-MHC transcripts become apparent Captopril treatment reduced skeletal actin transcripts and reversed the increase in beta-MHC that occurred with ageing.