| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Departments of Internal Medicine and of Physiology and Biophysics
2 Genetics Program, University of Iowa College of Medicine, Iowa City, Iowa 52242
3 The Population Council, The Rockefeller University, New York, New York 10021
Davisson, Robin L., Yueming Ding, David E. Stec, James F. Catterall, and Curt D. Sigmund. Novel mechanism of hypertension revealed by cell-specific targeting of human angiotensinogen in transgenic mice. Physiol. Genomics 1: 3–9, 1999.—We tested the hypothesis that the tissue-specific intrarenal renin-angiotensin system (RAS) can participate in the regulation of blood pressure independently of its endocrine counterpart, by generating two transgenic models that differ in their tissue-specific expression of human angiotensinogen (AGT). Human AGT expression was driven by its endogenous promoter in the systemic model and by the kidney androgen-regulated protein promoter in the kidney-specific model. Using molecular, biochemical, and physiological measurements, we demonstrate that human AGT mRNA and protein are restricted to the kidney in the kidney-specific model. Plasma ANG II was elevated in the systemic model but not in the kidney-specific model. Nevertheless, blood pressure was markedly elevated in both the systemic and kidney-specific transgenic mice. Acute administration of the selective ANG II AT-1 receptor antagonist losartan lowered blood pressure in the systemic model but not in the kidney-specific model. These results provide evidence for the potential importance of the intrarenal RAS in blood pressure regulation by showing that expression of AGT specifically in the kidney leads to chronic hypertension independently of the endocrine RAS.
transgenic mice; blood pressure regulation; renal function; angiotensin II
This article has been cited by other articles:
|
|
 |
|
  H. A. Shaltout, J. P. Figueroa, J. C. Rose, D. I. Diz, and M. C. Chappell Alterations in Circulatory and Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Fetal Programmed Hypertension Hypertension, February 1, 2009; 53(2): 404 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Sigmund A growing chain of evidence linking genetic variation in angiotensinogen with essential hypertension: focus on "A haplotype of human angiotensinogen gene containing -217A increases blood pressure in transgenic mice compared with -217G," by Jain et al. Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1846 - R1848. [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Dickson, X. Tian, X. Liu, D. R. Davis, and C. D. Sigmund Upstream Stimulatory Factor Is Required for Human Angiotensinogen Expression and Differential Regulation by the A-20C Polymorphism Circ. Res., October 24, 2008; 103(9): 940 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, X. Zhou, D. R. Davis, D. Xu, and C. D. Sigmund An androgen-inducible proximal tubule-specific Cre recombinase transgenic model Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1481 - F1486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobori, A. Katsurada, K. Miyata, N. Ohashi, R. Satou, T. Saito, Y. Hagiwara, K. Miyashita, and L. G. Navar Determination of plasma and urinary angiotensinogen levels in rodents by newly developed ELISA Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1257 - F1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kobori, M. Nangaku, L. G. Navar, and A. Nishiyama The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease Pharmacol. Rev., September 1, 2007; 59(3): 251 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobori, Y. Ozawa, R. Satou, A. Katsurada, K. Miyata, N. Ohashi, N. Hase, Y. Suzaki, C. D. Sigmund, and L. G. Navar Kidney-specific enhancement of ANG II stimulates endogenous intrarenal angiotensinogen in gene-targeted mice Am J Physiol Renal Physiol, September 1, 2007; 293(3): F938 - F945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Grigore, N. B. Ojeda, E. B. Robertson, A. S. Dawson, C. A. Huffman, E. A. Bourassa, R. C. Speth, K. B. Brosnihan, and B. T. Alexander Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R804 - R811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Dickson, M. B. Zimmerman, K. Rahmouni, and C. D. Sigmund The -20 and -217 Promoter Variants Dominate Differential Angiotensinogen Haplotype Regulation in Angiotensinogen-Expressing Cells Hypertension, March 1, 2007; 49(3): 631 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Lalouel and A. Rohrwasser Genetic Susceptibility to Essential Hypertension: Insight From Angiotensinogen Hypertension, March 1, 2007; 49(3): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Ojeda, D. Grigore, L. L. Yanes, R. Iliescu, E. B. Robertson, H. Zhang, and B. T. Alexander Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R758 - R763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Shaltout, B. M. Westwood, D. B. Averill, C. M. Ferrario, J. P. Figueroa, D. I. Diz, J. C. Rose, and M. C. Chappell Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II Am J Physiol Renal Physiol, January 1, 2007; 292(1): F82 - F91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-F. Guo, I. Chenier, J. L. Lavoie, J. S.D. Chan, P. Hamet, J. Tremblay, X. M. Chen, D. H. Wang, and T. Inagami Development of Hypertension and Kidney Hypertrophy in Transgenic Mice Overexpressing ARAP1 Gene in the Kidney Hypertension, September 1, 2006; 48(3): 453 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Dickson and C. D. Sigmund Genetic Basis of Hypertension: Revisiting Angiotensinogen Hypertension, July 1, 2006; 48(1): 14 - 20. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sethi, S. Iida, C. D. Sigmund, and D. D. Heistad Renal Thrombotic Microangiopathy in a Genetic Model of Hypertension in Mice Experimental Biology and Medicine, February 1, 2006; 231(2): 196 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Alexander Fetal programming of hypertension Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R1 - R10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hashimoto, J. W. Adams, K. E. Bernstein, and J. Schnermann Micropuncture determination of nephron function in mice without tissue angiotensin-converting enzyme Am J Physiol Renal Physiol, March 1, 2005; 288(3): F445 - F452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sherrod, X. Liu, X. Zhang, and C. D. Sigmund Nuclear localization of angiotensinogen in astrocytes Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R539 - R546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Loghman-Adham, C. E. Soto, T. Inagami, and L. Cassis The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease Am J Physiol Renal Physiol, October 1, 2004; 287(4): F775 - F788. [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]
|
|
|
|
|
|
H. Kobori, M. C. Prieto-Carrasquero, Y. Ozawa, and L. G. Navar AT1 Receptor Mediated Augmentation of Intrarenal Angiotensinogen in Angiotensin II-Dependent Hypertension Hypertension, May 1, 2004; 43(5): 1126 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Bianco, H. L. Keen, J. L. Lavoie, and C. D. Sigmund Untraditional methods for targeting the kidney in transgenic mice Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1027 - F1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Cole, N. Khokhlova, R. L. Sutliff, J. W. Adams, K. M. Disher, H. Zhao, M. R. Capecchi, P. Corvol, and K. E. Bernstein Mice Lacking Endothelial ACE: Normal Blood Pressure With Elevated Angiotensin II Hypertension, February 1, 2003; 41(2): 313 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobori, A. Nishiyama, L. M. Harrison-Bernard, and L. G. Navar Urinary Angiotensinogen as an Indicator of Intrarenal Angiotensin Status in Hypertension Hypertension, January 1, 2003; 41(1): 42 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dodic, T. Abouantoun, A. O'Connor, E. M. Wintour, and K. M. Moritz Programming Effects of Short Prenatal Exposure to Dexamethasone in Sheep Hypertension, November 1, 2002; 40(5): 729 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lantelme, A. Rohrwasser, B. Gociman, E. Hillas, T. Cheng, G. Petty, J. Thomas, S. Xiao, T. Ishigami, T. Herrmann, et al. Effects of Dietary Sodium and Genetic Background on Angiotensinogen and Renin in Mouse Hypertension, May 1, 2002; 39(5): 1007 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Glueck and V. J. Dzau Physiological Genomics: Implications In Hypertension Research Hypertension, February 1, 2002; 39(2): 310 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Navar, L. M. Harrison-Bernard, A. Nishiyama, and H. Kobori Regulation of Intrarenal Angiotensin II in Hypertension Hypertension, February 1, 2002; 39(2): 316 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Stec, H. L. Keen, and C. D. Sigmund Lower Blood Pressure in Floxed Angiotensinogen Mice After Adenoviral Delivery of Cre-Recombinase Hypertension, February 1, 2002; 39(2): 629 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. PENTZ, M. L. S. S. LOPEZ, H.-S. KIM, O. CARRETERO, O. SMITHIES, and R. A. GOMEZ Ren1d and Ren2 cooperate to preserve homeostasis: evidence from mice expressing GFP in place of Ren1d Physiol Genomics, June 6, 2001; 6(1): 45 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobori, L. M. Harrison-Bernard, and L. G. Navar Enhancement of Angiotensinogen Expression in Angiotensin II-Dependent Hypertension Hypertension, May 1, 2001; 37(5): 1329 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Stec and C. D. Sigmund Physiological Insights from Genetic Manipulation of the Renin-Angiotensin System Physiology, April 1, 2001; 16(2): 80 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L G. Navar, K. D Mitchell, L. M Harrison-Bernard, H. Kobori, and A. Nishiyama Review: Intrarenal angiotensin II levels in normal and hypertensive states Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S176 - S184. [PDF]
|
|
|
|
|
|
Y. Ding and C. D. Sigmund Androgen-dependent regulation of human angiotensinogen expression in KAP-hAGT transgenic mice Am J Physiol Renal Physiol, January 1, 2001; 280(1): F54 - F60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. SINN and C. D. SIGMUND Identification of three human renin mRNA isoforms from alternative tissue-specific transcriptional initiation Physiol Genomics, June 29, 2000; 3(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Sinn, D. R. Davis, and C. D. Sigmund Highly Regulated Cell Type-restricted Expression of Human Renin in Mice Containing 140- or 160-Kilobase Pair P1 Phage Artificial Chromosome Transgenes J. Biol. Chem., December 10, 1999; 274(50): 35785 - 35793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rohrwasser, T. Morgan, H. F. Dillon, L. Zhao, C. W. Callaway, E. Hillas, S. Zhang, T. Cheng, T. Inagami, K. Ward, et al. Elements of a Paracrine Tubular Renin-Angiotensin System Along the Entire Nephron Hypertension, December 1, 1999; 34(6): 1265 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ding, D. E. Stec, and C. D. Sigmund Genetic Evidence That Lethality in Angiotensinogen-deficient Mice Is Due to Loss of Systemic but Not Renal Angiotensinogen J. Biol. Chem., March 2, 2001; 276(10): 7431 - 7436. [Abstract] [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 |
