| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print March 26, 2002
Physiol Genomics, 10.1152/physiolgenomics.00007.2002
Submitted on January 29, 2002
Accepted on March 26, 2002
1 Internal Medicine, University of Iowa, Iowa City, IA, USA
2 Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USA
3 Internal Medicine, University of Iowa, Iowa City, IA, USA; Physiology and Biophysics, University of Iowa, Iowa City, IA, USA
* To whom correspondence should be addressed. E-mail: curt-sigmund{at}uiowa.edu.
The brain renin-angiotensin system (RAS) has an important role in the regulation of cardiovascular function. In the brain, angiotensinogen (AGT) is expressed mainly in astrocytes (glia) and in some neurons in regions controlling cardiovascular activities. Due to the inability to dissect the functional role of astrocyte- versus neuron-derived AGT in vivo by pharmacological approaches, the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and fluid and electrolyte balance remains unclear. Therefore, we generated a transgenic mouse model over-expressing human AGT under the control of a neuron-specific (synapsin I) promoter (SYN-hAGT). These mice exhibited high level expression of human AGT mRNA in the brain, with lower expression in the kidney and heart. Human AGT was not detected in plasma, but in the brain was expressed exclusively in neurons. Intracerebroventricular (30 ng) but not intravenous (500 ng) injection of purified human renin caused a pressor response, which was prevented by ICV pre-injection of the angiotensin II type 1 receptor antagonist losartan, indicating an AT-1 receptor dependent functional role of neuron-derived AGT in the regulation of BP in response to exogenous REN. Double transgenic mice expressing both the human renin gene and SYN-hAGT transgene exhibited normal BP and water intake, but had an increased preference for salt. These data suggest that neuronal AGT may play an important role in regulating salt intake and salt appetite.
This article has been cited by other articles:
|
|
 |
|
  J. L. Grobe, D. Xu, and C. D. Sigmund An Intracellular Renin-Angiotensin System in Neurons: Fact, Hypothesis, or Fantasy Physiology, August 1, 2008; 23(4): 187 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sakima, D. B. Averill, S. O. Kasper, L. Jackson, D. Ganten, C. M. Ferrario, P. E. Gallagher, and D. I. Diz Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1412 - H1419. [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]
|
|
|
|
 |
|
 K. Sakai, M. W. Chapleau, S. Morimoto, M. D. Cassell, and C. D. Sigmund Differential modulation of baroreflex control of heart rate by neuron- vs. glia-derived angiotensin II Physiol Genomics, December 15, 2004; 20(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Lavoie, K. D. Lake-Bruse, and C. D. Sigmund Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule Am J Physiol Renal Physiol, May 1, 2004; 286(5): F965 - F971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Lavoie, M. D. Cassell, K. W. Gross, and C. D. Sigmund Adjacent Expression of Renin and Angiotensinogen in the Rostral Ventrolateral Medulla Using a Dual-Reporter Transgenic Model Hypertension, May 1, 2004; 43(5): 1116 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Lavoie, M. D. Cassell, K. W. Gross, and C. D. Sigmund Localization of renin expressing cells in the brain, by use of a REN-eGFP transgenic model Physiol Genomics, January 15, 2004; 16(2): 240 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Davisson Physiological genomic analysis of the brain renin-angiotensin system Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R498 - R511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Lavoie and C. D. Sigmund Minireview: Overview of the Renin-Angiotensin System--An Endocrine and Paracrine System Endocrinology, June 1, 2003; 144(6): 2179 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Skott Angiotensin II and control of sodium and water intake in the mouse Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1380 - R1381. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Morimoto, M. D. Cassell, and C. D. Sigmund Glia- and Neuron-specific Expression of the Renin-Angiotensin System in Brain Alters Blood Pressure, Water Intake, and Salt Preference J. Biol. Chem., August 30, 2002; 277(36): 33235 - 33241. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
