© 2002 American Heart Association, Inc.
Editorials |
It’s Renin in the Brain
Transgenic Animals Elucidate the Brain Renin-Angiotensin System
From the Max-Delbrück-Center for Molecular Medicine (M.B., D.G.), Berlin-Buch, Germany; and the Department of Clinical Pharmacology (D.G.), University Hospital Benjamin Franklin, Free University, Berlin, Germany.
Correspondence to Prof Dr Detlev Ganten, Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str 10, D-13092 Berlin-Buch, Germany. E-mail ganten@mdc-berlin.de
Key Words: renin-angiotensin system • brain • central mechanisms • transgenic animals
Since the first description of renin, angiotensinogen and angiotensin as well as converting enzyme and angiotensin receptors in the brain exactly 30 years ago,1–5 there was a heated debate, whether an endogenous intrinsic brain renin- angiotensin system (RAS) exists or not.6,7 For a long time, the "believers" of local angiotensin II generation by the brain RAS were in a minority. Even at a symposium 1981, celebrating the 10-year anniversary of the discovery of the brain RAS, there was skepticism and the question whether the "renin-like" enzyme in brain was identical with cathepsins, tonin, or other proteases was a matter of debate. Historically, it is interesting that the presence in the brain of other classically peripheral peptides such as insulin, glucagon, and substance P was accepted without identification of the local synthetic pathway and less controversial than angiotensin as neuropeptide. Open letters, public debates, and personal accusations nourished sometimes emotional controversy whether angiotensin could be generated locally in tissue. The brain was a model for angiotensin generating pathways in other extrarenal tissues because the blood-brain barrier, which is impermeable for proteins and peptides, made it more unlikely that the RAS components measured in the brain were contaminations from the plasma.
Angiotensin has extremely powerful effects on the brain that synergistically increase blood volume and blood pressure, eg, by stimulation of water intake and salt appetite, release of various pituitary hormones, increase of sympathetic tone, and decrease of baroreceptor reflex.7 The local generation of angiotensin II in the brain by an endogenous
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