The human placental renin-angiotensin system

The human placenta and related tissues are considered to be examples of the recently accepted local renin–angiotensin systems (RAS). The brain is another example of a system that is thought to be regulated independently of the kidney and the role of angiotensin within the CNS as a neural mediator has drawn considerable attention. It has been known for a long time that many of the neuroendocrine mediators and receptors are expressed in the placenta and it has been suggested that there are many parallels between the classical neuroendocrine system and the placental one. The present review summarizes information that components of the RAS are expressed in uteroplacental tissues, are regulated by endogenous substances, and have important biological functions within this reproductive system. A comparison of similarities and differences between the classical and the placental RAS may provide clues to functions in other endocrine and neuroendocrine systems. The major components of the placental RAS that are considered are renin, prorenin, angiotensin I, angiotensin II, angiotensin converting enzyme (ACE), angiotensin receptors, and angiotensinogen (renin substrate). The factors that regulate these components at the cellular and the nuclear level are described. It is concluded that prorenin via angiotensin-dependent and angiotensin-independent mechanisms influences functions within uteroplacental tissues. Some of these actions are direct and others are mediated by the release of different signalling molecules. These features are similar to many neuroendocrine systems and utilize some of the same messengers.