The amount of fluid in our body, which has a major influence on blood pressure, is regulated by a combination of molecules that comprise the renin-angiotensin system (RAS).
The RAS is active in both the kidney and brain, but the mechanisms that control the RAS in the brain had not well defined until researchers from the University of Iowa, Iowa City, showed that in mice the RAS is active in a region of the brain known as the subfornical organ (SFO) and that RAS activity in the SFO drives increased consumption of water and salt.
The molecule that causes most of the effects of the RAS is angiotensin II, which is generated from angiotensinogen by renin and ACE. In their study, which appears in the April issue of the Journal of Clinical Investigation, Curt Sigmund and colleagues generated mice expressing human renin and human angiotensinogen in the brain of mice.
These mice consumed more water and salt than normal mice and this increased consumption could be reversed by the administration of an inhibitor of the angiotensin II receptor into the brain. Furthermore, production of angiotensin II was specifically detected in the SFO and eliminating the expression of human angiotensinogen in the SFO reversed the increased water and salt consumption. This study indicates that the production of angiotensin II in the SFO has an important role in regulating water intake, and therefore the amount of fluid in the body.
As discussed in an accompanying commentary by Kelly Parsons and Thomas Coffman, these data suggest that RAS activity in the SFO and kidney are nonredundant and that "creative use of techniques allowing for cell- and tissue-specific manipulation of gene expression in vivo" are necessary to determine further the extent of functional and regulatory overlap between RAS activity in the SFO and brain.
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