The increased cardiac preload caused by neurohumoral compensatory mechanisms (angiotensin, catecholamines, and aldosterone) will evoke intrinsic cardiac compensation, also known as remodelling. Dilation of the heart and myocardial cell hypertrophy is an adaptation in order to maintain cardiac output and to reduce ventricular wall tension. Angiotensin II binds to AT1 and AT2receptors present on cardiac muscle and fibroblasts. Stimulated AT2 receptors induce the release of collagenase. This enzyme cuts collagen between the muscle bundles, which are stretched due to the high ventricular pressure. The loose muscle bundles make dilation of the heart possible. AT1 receptors now stimulate the production of collagen. The muscle bundles are attached to each other again in a new setting and the dilated heart now has a thinner wall.
Because the pressure in the ventricle remains the same, there is an increase in tension/surface area of the wall. This and angiotensin II are responsible for increased protein production by the myocardial cells and thus hypertrophy at the cellular level. Growth factors are thought to mediate the remodelling process: transforming growth factor beta (TGF-β) is a common downstream target of the signal transduction cascade initiated by catecholamines and angiotensin II epidermal growth factor (EGF) is a target of the signalling pathway activated by aldosterone The compensatory mechanisms result in positive inotropy by increasing contractility, increased efficiency in systolic emptying and reduced diastolic emptying. However, the chronic activation of these compensatory mechanisms will eventually damage the heart.
Remodelling consists of