Role of Angiotensin II in Hypertension-Induced Cardiac Hypertrophy and Failure

Besides playing a role in blood-pressure regulation and salt and fluid homeostasis, the octapeptide angiotensin II mediates cell growth and differentiation. Its effects are dependent on angiotensin receptors, of which both AT1 and AT2 receptors are extensively described. In cardiac hypertrophy and heart failure, angiotensin receptors are differentially regulated. It is established that AT1 receptors induce cell growth, while AT2 receptors have been associated with growth inhibition, differentiation, and apoptosis. The availability of receptors controlling cell function within a broad spectrum for a single hormone and the regulation of these receptors during cardiac hypertrophy and failure emphasize a complex role for angiotensin II in cardiac pathogenesis. Due to their functional properties, AT1 and AT2 receptors might counteract each other in cell growth processes. Therefore, the current clinical use of specific AT1 receptor antagonists raises questions as to the role of the AT2 receptor in disease processes such as cardiac hypertrophy and failure. Under AT1 receptor antagonist treatment, AT2 receptors are overexposed to angiotensin II. This article describes a possible role of angiotensin II through its angiotensin receptors AT1 and AT2 in cardiac hypertrophy and heart failure.