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There are significant gender differences in the LV adaptation to pressure overload despite a similar degree of LVH and systolic wall stress in male and female rats. There is the potential for estrogen signaling through the adult myocyte estrogen receptor in both male and female rats to contribute to gender differences in gene expression in pathologic hypertrophy.

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Abstract-Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. ] o , 25°C), the amplitude of myocyte shortening and peak-systolic [Ca 2ϩ ] i in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca 2ϩ ] i transients were slower. In response to the challenge of high [Ca 2ϩ ] o , fractional cell shortening was severely depressed with reduced peak-systolic [Ca 2ϩ ] i in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca 2ϩ ] i increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca 2ϩ ] o and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na ϩ -Ca 2ϩ exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca 2ϩ -ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca 2ϩ load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca 2ϩ ] i and SR Ca 2ϩ load and simulates findings in human failing myocytes. (Circ Res. 2000;87:588-595.) Key Words: myocytes Ⅲ contractility Ⅲ sarcoplasmic reticulum Ⅲ Ca 2ϩ -ATPase Ⅲ heart failure Ⅲ hypertrophy T he regulation of contractility is under intense investigation with the use of transgenic mice. 1,2 The mouse cardiovascular system differs from that of humans and larger mammals, including the rapid heart rate, faster myofibrillar ATPase activity and sarcoplasmic reticulum (SR) Ca 2ϩ uptake, 2,3 and higher mechanical performance per unit ventricular mass. 4 To interpret findings in genetically manipulated mice, it is critical to understand the properties of normal mouse myocyte contractility and the changes induced by clinically relevant stimuli such as chronic load. We reported that mice with ascending aortic stenosis (AS) develop compensated hypertrophy (4-week AS) and the later stage of early heart failure (7-week AS). 4,5 The aim of the present study was to examine contractile reserve in myocytes from AS mice in transition from hypertrophy to early heart failure. We measured myocyte contraction and [Ca 2ϩ ] i transients in left ventricular (LV) myocytes from normal, 4-week AS, and 7-week AS mice in response to the challenge of stepped increases in [Ca 2ϩ ] o . In separate experiments, we examined the response to rapid pacing stimulation. Although only subtle abnormalities in the time course of contraction and the [Ca 2ϩ ] i transients are present at baseline, contractile reserve is depressed in ...