Role of neurohormones in ventricular adaptation and failure

When the heart faces a hemodynamic challenge (pressure or volume overload, myocardial infarction, etc.), mechanical, neurohormonal, and metabolic changes occur and impact on the myocytes, the fibroblasts, and the microcirculation. These changes immediately modify the function of the heart but also trigger gene expression and protein synthesis, leading after days and months to a remodeled heart in which not only the geometry of the cavity is changed but the composition of the wall has also become markedly abnormal. The remodeling process is infinitely complex, because all factors involved interact in a complex way and because the genetic responses may vary between species and between individuals. Moreover, we still ignore the role (or even the existence) of many growth factors involved in the process. To illustrate this complexity, one can use 2 classic models: pressure-overload hypertrophy and acute myocardial infarction. In both situations, experimental models can be designed so that angiotensin II and aldosterone are elevated and in both types of models the use of an angiotensin-converting enzyme inhibitor favorably influences hypertrophy and survival. Interestingly, however, intense interstitial fibrosis leading to an increase in diastolic stiffness is present in the pressure overload models, whereas increased diastolic distensibility and cardiac dilation are observed in models of myocardial infarction. This clearly indicates that in addition to the renin-angiotensin system other factors interact in the remodeling process and modulate the effects of angiotensin-converting enzyme inhibition on ventricular remodeling.