The renin-angiotensin system is highly conserved through evolutionary history, and has multiple functions in addition to
maintaining cardiovascular homeostasis: these include the regulation of renal cell survival and cell death, and development of the kidney.
The importance of angiotensin (ANG) in normal kidney development was first recognized in infants with renal maldevelopment born to
mothers treated with angiotensin converting enzyme (ACE) inhibitors or with ANG AT1 receptor blockers. The molecular role of ANG
in renal development has been elucidated using gene targeting in mice, revealing major effects in branching morphogenesis,
vasculogenesis, development of the papilla and renal concentrating mechanism. Although exposure of the fetus to ANG inhibitors is
potentially harmful throughout pregnancy, effects are greater in late compared to early gestation. Significant differences between humans
and rodents in placental transfer of ANG and timing of renal development contributed to initial delays in recognizing the teratogenic
effects of ANG inhibitors. Although administration of ACE or AT1 receptor inhibitors can slow progression of renal disease in older
children, ANG inhibition in the neonatal period can aggravate renal injury due to congenital urinary tract obstruction. Neonates are also
far more sensitive than older children to the hypotensive actions these agents and doses must be markedly reduced to avoid precipitating
oliguria. Understanding the complex interactions of the maturing renin-angiotensin system in the perinatal period is essential in the use of
ANG or renin inhibitors in women during childbearing years or in neonates with cardiovascular or renal disease.
Keywords: Angiotensin, anomalies, development, fetus, hypertension, kidney, neonate, Renal Impairment, Pharmacologic Inhibition, renin-angiotensin.
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