| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Max Delbrück Center for Molecular Medicine, 13092 Berlin; 3 Department of Clinical Pharmacology, University Hospital Benjamin Franklin, Free University Berlin, 12200 Berlin, Germany; and 2 Institut National de la Santé et de la Recherche Médicale Unité 331, 69675 Bron, France
TGR(ASrAOGEN)680, a newly developed transgenic rat line with specific downregulation of astroglial synthesis of angiotensinogen, exhibits decreased brain angiotensinogen content associated with a mild diabetes insipidus and lower blood pressure. Autoradiographic experiments were performed on TGR(ASrAOGEN) (TG) and Sprague-Dawley (SD) control rats to quantify AT1 and AT2 receptor-binding sites in different brain nuclei and circumventricular organs. Dose-response curves for drinking response to intracerebroventricular injections of ANG II were compared between SD and TG rats.
In most of the regions inside the blood-brain barrier [paraventricular nucleus (PVN), piriform cortex, lateral olfactory tract (LOT), and lateral preoptic area (LPO)], AT1 receptor binding (sensitive to CV-11974) was significantly higher in TG compared with SD. In contrast, in the circumventricular organs investigated [subfornical organ (SFO) and area postrema], AT1 receptor binding was significantly lower in TG. AT2 receptors (binding sensitive to PD-123319) were detected at similar levels in the inferior olive (IO) of both strains. Angiotensin-binding sites sensitive to both CV-11974 and PD-123319 were detected in the LPO of SD rats and specifically upregulated in LOT, IO, and most notably PVN and SFO of TG. The dose-response curve for water intake after intracerebroventricular injections showed a higher sensitivity to ANG II of TG (EC50 = 3.1 ng) compared with SD (EC50 = 11.2 ng), strongly suggesting that the upregulation of AT1 receptors inside the blood-brain barrier of TG rats is functional.
Finally, we showed that downregulation of angiotensinogen synthesized by astroglial cells differentially regulates angiotensin receptor subtypes inside the brain and in circumventricular organs.
antisense; angiotensin receptor subtypes
This article has been cited by other articles:
|
|
 |
|
  A. C. Arnold, A. Sakima, D. Ganten, C. M. Ferrario, and D. I. Diz Modulation of Reflex Function by Endogenous Angiotensins in Older Transgenic Rats With Low Glial Angiotensinogen Hypertension, May 1, 2008; 51(5): 1326 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Campos, R. Iliescu, M. A. P. Fontes, W.-P. Schlegel, M. Bader, and O. C. Baltatu Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2371 - H2376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sherrod, D. R. Davis, X. Zhou, M. D. Cassell, and C. D. Sigmund Glial-specific ablation of angiotensinogen lowers arterial pressure in renin and angiotensinogen transgenic mice Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1763 - R1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. O. Kasper, C. S. Carter, C. M. Ferrario, D. Ganten, L. F. Ferder, W. E. Sonntag, P. E. Gallagher, and D. I. Diz Growth, metabolism, and blood pressure disturbances during aging in transgenic rats with altered brain renin-angiotensin systems Physiol Genomics, November 17, 2005; 23(3): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Skott Body sodium and volume homeostasis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R14 - R18. [Full Text] [PDF]
|
|
|
|
|
|
T. E. Lohmeier Neurohumoral regulation of arterial pressure in hemorrhage and heart failure Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R810 - R814. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bader and D. Ganten It's Renin in the Brain: Transgenic Animals Elucidate the Brain Renin-Angiotensin System Circ. Res., January 11, 2002; 90(1): 8 - 10. [Full Text] [PDF]
|
|
|
|
|
|
S. Morimoto, M. D. Cassell, T. G. Beltz, A. K. Johnson, R. L. Davisson, and C. D. Sigmund Elevated Blood Pressure in Transgenic Mice With Brain-Specific Expression of Human Angiotensinogen Driven by the Glial Fibrillary Acidic Protein Promoter Circ. Res., August 17, 2001; 89(4): 365 - 372. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
