NORMAL AND HYPERTROPHIED SENESCENT RAT-HEART - MECHANICAL AND MOLECULAR CHARACTERISTICS

The energetics of the senescent (S) rat heart and the mechanisms by which it adapts to pressure overload have been investigated by simultaneous cardiac mechanical, energetic, and molecular biological studies. Compared with young adult (YA), S papillary muscles had an improved economy of contraction since the curvature (G) of Hill's (Proc. R. Soc. Lond. B. Biol. Sci. 126: 136-195, 1938) hyperbola was increased (S, 1.93 +/- 0.13; YA, 1.60 +/- 0.07, P < 0.05). In addition, the maximum unloaded shortening (V(max)) and relengthening velocities were both reduced in S. In parallel, both alpha-myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca2+-adenosinetriphosphatase (ATPase) mRNA contents were reduced (-30 and -28%, respectively), whereas beta-MHC mRNA was increased (+91%). The active tension (S, 40.0 +/- 2.6; YA, 50.1 +/- 2.5 mN/mm2, P < 0.01) was depressed although the active force remained unchanged (S, 52.0 +/- 4.0; YA, 47.5 +/- 2.5 mN). Pressure overload in senescent deoxycorticosterone acetate (DOCA)-salt rats induced a left ventricular hypertrophy (+43%) and a further decrease in both V(max) (S, 2.81 +/- 0.10; DOCA-salt, 2.55 +/- 0.13 initial length corresponding to peak of length-active curve/s, P < 0.05) and alpha-MHC mRNA (-30%) content. Senescence modifies mechanics and gene expression in a way similar to pressure overload. During senescence, an additional overload induces left ventricular hypertrophy and attenuates V(max) without worsening the economy of the contraction.