Published online before print December 27, 2005, doi: 10.1161/01.HYP.0000200278.64801.4e
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(Hypertension. 2006;47:145.)
© 2006 American Heart Association, Inc.
Editorial Commentaries |
Targeting Brain AT1 Receptors By RNA Interference
From the Departments of Internal Medicine (C.D.S.); Physiology & Biophysics (C.D.S.); and Department of Anatomy and Cell Biology (R.L.D.), Roy J. and Lucille A. Carver College of Medicine; University of Iowa, Iowa City.
Correspondence to Curt D. Sigmund, PhD., Departments of Internal Medicine and Physiology & Biophysics, 3181B Medical Education and Biomedical Research Facility, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242. E-mail curt-sigmund@uiowa.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The dipsogenic and pressor actions of angiotensin II (Ang II) in the central nervous system (CNS) have been well documented in many species and are now accepted as dogma. The major central cardiovascular effects of Ang II are elicited by a complex receptor-dependent signaling cascade initiated by the detection of circulating Ang II in regions of the brain lacking a blood brain barrier (BBB) through local production of Ang II in regions outside and inside the BBB or through the neurotransmitter actions of Ang II. It is generally accepted that most of the central neurocardiovascular actions of Ang II occur through the activation of intracellular signaling cascades that originate at the Ang II type 1 (AT1) receptor. A second Ang II receptor, termed AT2, has been implicated in some cardiovascular and behavioral responses. However, the AT2 receptor is distantly related to AT1 and can be effectively distinguished from AT1 pharmacologically.
In humans, a single gene encodes the AT1 Ang II receptor, whereas in rodents a duplication resulted in 2 AT1 receptor genes, located on different chromosomes, each known to encode 1 of 2 distinct subtypes of the receptor, AT1a and AT1b. Both receptors are highly homologous, use the same signaling mechanisms, and cannot be distinguished using currently available pharmacological reagents or antisera. Despite their high similarity at the protein level, sufficient divergence is present in the sequence of the mRNA that allows them to be distinguished by RT-PCR and in situ hybridization. Through this analysis, it has
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