Angiotensin type 1 and type 2 receptors during ontogeny: cardiovascular and renal effects

The renin-angiotensin system (RAS) is a major component of cardiovascular and renal homeostasis, maintaining blood pressure and water and electrolyte balance in health and disease. Whilst knowledge regarding the RAS in adult organisms has substantially increased over the last three decades, physiological effects and levels of functioning of the system during the perinatal period are poorly understood. It has been shown, however, that the RAS is subject to remarkable developmental changes that involve all system components, including the main active biologic peptide, angiotensin II (Ang II) and the receptors through which these effects are mediated, type 1 receptors (AT1Rs) and type 2 receptors (AT2Rs). The pattern of developmental changes suggests a relevant physiological role for the RAS in the critical cardio-renal adaptations to life after birth. In adulthood, the majority of the physiological functions of Ang II are mediated by activation of AT1Rs, whilst the roles for AT2Rs are less clear. Although the integrity of the AT1R signalling pathway is a pre-requisite for normal renal development, the physiological effects mediated by A1TRs during ontogeny are not well characterized. Much less is known regarding the roles that AT2Rs may play in regulating cardio-renal homeostasis in the newborn, despite the fact that the RAS appears to be a major player in fetal programming of disease. This article reviews current knowledge regarding the temporal and spatial expression pattern of ATRs during ontogeny, the cardiovascular and renal effects mediated by the ATRs early in life, as well as the clinical relevance for ATRs in the newborn period.