REGIONAL MYOSIN HEAVY-CHAIN EXPRESSION IN VOLUME AND PRESSURE-OVERLOAD INDUCED CARDIAC-HYPERTROPHY

Although the overall shift towards the V-3 myosin heavy chain (MHC) ha s been shown to be associated with cardiac hypertrophy, quantitative e vidence describing regional expression is sparse. The aim of this stud y was to compare and contrast the regional ventricular myosin isoform expression in two distinct haemodynamic states: pressure and volume ov erload. Volume overload was achieved using an aortocaval fistula (ACF) model and pressure overload by two-kidney-one-clip (2K1C) hypertensio n. A separate group (UC-2K1C) had the clip removed 1 week prior to inv estigation. Sham operated rats (SHAM) served as controls. All groups w ere studied 4 weeks after surgery. Ventricular tissue samples (approxi mate to 50 mg) were taken from the walls of the right ventricle (RV), septum and left ventricular (LV) free wall. Tissue samples (excluding RV) were divided into endocardium and epicardium, and myosin expressio n was determined using polyacrylamide gel electrophoresis. Cardiac hyp ertrophy was substantial in both LV (1.7-fold) and RV (1.9-fold) in AC F rats. The 2K1C rats had similar LV enlargement (1.6-fold) whereas RV hypertrophy was not as great (1.2-fold). Blood pressure (BP) was incr eased 65% in 2K1C rats, whereas there was no change in ACF rats with r espect to SHAM animals. After unclipping (UC-2K1C), LV hypertrophy and BP had returned towards control levels. In general, V-3 MHC expressio n was associated with increasing LV hypertrophy in both 2K1C and ACF m odels. However, there was a marked endo-epi differential (1.5:1) in th e LV free wall and septum of 2K1C rats. In contrast, in ACF rats there was no differential V-3 MHC expression in the LV or septal tissue, i. e. expression was similar in both endo- and epi-samples. Elevated expr ession of V-3 MHC persisted despite normotension and regression of car diac hypertrophy in UC-2K1C rats. Taken together with published result s demonstrating that relative transmural myocyte hypertrophy in ACF ra ts (endo > epi) is in contrast to that seen in 2K1C rats (epi > endo), the present findings reveal; that regional V-3 myosin expression repr esents a distinct adaptational component of the overall cardiac hypert rophic response in both volume and pressure overload.