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Ca2+-dependent heterometric and homeometric autoregulation in hypertrophied rat heart.

There is evidence to suggest that the alterations in cardiac function that accompany several forms of myocardial hypertrophy are due in part to desensitization of the heart to the positive inotropic effect of extracellular Ca2+ (Cae2+). In this study the heterometric and homeometric functional responsiveness of normal (SH) and hypertrophied (HYP) isolated working rat hearts was examined as a function of extracellular Ca2+ concentration [( Ca2+]e). Surgically induced renovascular hypertension was used to produce a 39% increase in left ventricular (LV) weight in HYP hearts relative to LV weights of SH hearts. The Cae2+ dependence of heterometric autoregulation was examined in SH and HYP hearts. At high left atrial filling pressures, HYP hearts were functionally less sensitive to changes in [Ca2+]e than were SH hearts; this difference appeared to be due to a preload-dependent increase in the functional sensitivity of SH hearts but not HYP hearts to changes in [Ca2+]e. In both SH and HYP hearts, a step increase in afterload resulted in a beat-by-beat increase in peak aortic outflow systolic pressure (AoP) independent of changes in LV diastolic pressure. Under our experimental conditions, the magnitude of this homeometric AoP increase (the Anrep effect) was similar in both SH and HYP hearts. The AoP increase occurred at a monoexponential rate (kHA) and was much faster in SH than in HYP hearts. Furthermore, KHA varied directly as a function of [Ca2+]e only in the SH hearts.