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Ca2+-dependent heterometric and homeometric autoregulation in hypertrophied rat heart
D G Pawlush1, T I Musch, R L Moore
1Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Insights
Hypertrophied hearts show reduced sensitivity to extracellular calcium, impacting cardiac function. The Anrep effect, a response to increased afterload, is slower in hypertrophied hearts and calcium-dependent only in normal hearts.
Area of Science:
- Cardiovascular Physiology
- Cardiac Hypertrophy Research
- Calcium Signaling in the Heart
Background:
- Myocardial hypertrophy can alter cardiac function, potentially due to impaired response to extracellular calcium (Ca2+e).
- Understanding these alterations is crucial for managing heart conditions associated with hypertrophy.
Purpose of the Study:
- To investigate the functional responsiveness of normal (SH) and hypertrophied (HYP) isolated working rat hearts to varying extracellular calcium concentrations.
- To examine the influence of extracellular calcium on heterometric and homeometric cardiac adjustments in SH and HYP hearts.
Main Methods:
- Surgically induced renovascular hypertension created HYP rat hearts with increased left ventricular (LV) weight.
- Isolated working rat hearts (SH and HYP) were subjected to varying extracellular calcium concentrations ([Ca2+]e).
- Functional responsiveness was assessed by measuring changes in cardiac output and pressure under different preload and afterload conditions.
Main Results:
- Hypertrophied hearts exhibited reduced sensitivity to extracellular calcium, particularly at higher filling pressures, unlike normal hearts.
- The Anrep effect (homeometric autoregulation) magnitude was similar in SH and HYP hearts, but its rate (kHA) was significantly slower in HYP hearts.
- The rate of the Anrep effect (kHA) demonstrated a direct relationship with extracellular calcium concentration only in normal (SH) hearts.
Conclusions:
- Cardiac hypertrophy is associated with desensitization to the positive inotropic effects of extracellular calcium.
- The Anrep effect's rate is impaired in hypertrophied hearts and its calcium dependency is lost.
- These findings highlight altered calcium handling and responsiveness as key factors in the functional decline of hypertrophied hearts.
Abstract:
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.