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

The energetics of the senescent (S) rat heart and the mechanisms by wh ich it adapts to pressure overload have been investigated by simultane ous cardiac mechanical, energetic, and molecular biological studies. C ompared with young adult (YA), S papillary muscles had an improved eco nomy of contraction since the curvature (G) of Hill's (Proc. R. Soc. L ond. B. Biol. Sci. 126: 136-195, 1938) hyperbola was increased (S, 1.9 3 +/- 0.13; YA, 1.60 +/- 0.07, P < 0.05). In addition, the maximum unl oaded shortening (V(max)) and relengthening velocities were both reduc ed in S. In parallel, both alpha-myosin heavy chain (MHC) and sarcopla smic reticulum (SR) Ca2+-adenosinetriphosphatase (ATPase) mRNA content s 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 correspondi ng 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 overlo ad induces left ventricular hypertrophy and attenuates V(max) without worsening the economy of the contraction.