Tissue renin-angiotensin systems: fact or fiction?
The discovery of the components of the renin-angiotensin system (RAS) in various tissues gave rise to the idea that functional "tissue" RASs exist that are more or less independent of the hormonal RAS. Further support for this notion came from the recent demonstration of the mRNA for the protein components of the RAS in a number of organs. Last but not least, the introduction of the converting-enzyme (CE) inhibitors, generating an enormous scientific interest in the role of the RAS, has contributed to the concept of "tissue" RASs, since some of the effects of these drugs were thought to be reconciled better with "tissue" than with plasma RAS inhibition. However, this model of plasma vs. "tissue" RAS still suffers from a number of conceptual problems. For instance, with respect to the "tissue" RAS in the vascular wall, it is not clear at present whether angiotensin-converting enzyme (ACE) is at all active inside endothelial cells. In addition, all evidence available speaks against its localization in the vascular media, while there may be some activity of the enzyme in the adventitial layer. Concerning the heart, there is at present no unequivocal evidence for a local angiotensin II (Ang II) production through ACE in cardiac tissue outside the coronary vessels. The localization of Ang II generation within tissue RASs in the adrenal gland or in the kidney, where Ang II may be generated through CE at the tubular brush border, are far from being elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)
Unger
T
T
Department of Pharmacology, University of Heidelberg, Germany.
Gohlke
P
P
Paul
M
M
Rettig
R
R
D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*