(Hypertension. 1996;28:290-296.)
© 1996 American Heart Association, Inc.
Articles |
Regulation of Human Renin mRNA Expression and Protein Release in Transgenic Mice
the Departments of Pediatrics (M.W.T.), Internal Medicine (S.B.S., C.D.S.), and Physiology and Biophysics (C.D.S.), University of Iowa, Iowa City.
Correspondence to Mark W. Thompson, MD, Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC 20307.
The renin-angiotensin system plays a major role in the regulation of blood pressure and electrolyte homeostasis in mammals. In this study, we subjected transgenic mice containing a human renin genomic construct to a variety of pharmacological and physiological manipulations to test whether expression of the human renin gene and release of active human renin is appropriately regulated in this model. These manipulations were designed to test major regulators of renin release, including angiotensin II, the macula densa, renal perfusion pressure, and ß-adrenergic receptors. We used human plasma renin concentration and human renal renin mRNA levels to document the response of the transgene to these stimuli. Human plasma renin concentration increased in response to both angiotensin-converting enzyme inhibition with captopril and isoproterenol and decreased after a high salt diet. A low salt or sodium-deficient diet did not stimulate renin release. Human renin mRNA levels in kidney increased after captopril but were unchanged in the other experimental groups. We also measured the levels of human renin mRNA in double transgenic mice containing the same human renin gene in addition to the human angiotensinogen gene. These mice are chronically hypertensive and have increased circulating levels of angiotensin II. Human renin mRNA levels in the kidney were paradoxically elevated compared with their single transgenic normotensive counterparts. These transgenic mice provide a model for examination of human renin regulation and may help elucidate the molecular mechanisms that regulate the gene in response to physiological cues.
Key Words: renin-angiotensin system • genetics • gene expression regulation • mice, transgenic
This article has been cited by other articles:
 |
|
 |
|
  J. L. Lavoie, X. Liu, R. A. Bianco, T. G. Beltz, A. K. Johnson, and C. D. Sigmund Evidence Supporting a Functional Role for Intracellular Renin in the Brain Hypertension, March 1, 2006; 47(3): 461 - 466. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 S. Morimoto, M. D. Cassell, and C. D. Sigmund Neuron-specific expression of human angiotensinogen in brain causes increased salt appetite Physiol Genomics, May 10, 2002; 9(2): 113 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Lumbers, A. J. Gunn, D. Y. Zhang, J. J. Wu, L. Maxwell, and L. Bennet Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R1045 - R1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Keen and C. D. Sigmund Paradoxical Regulation of Short Promoter Human Renin Transgene by Angiotensin II Hypertension, February 1, 2001; 37(2): 403 - 407. [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]
|
|
|
|
|
|
P. L. Sinn, X. Zhang, and C. D. Sigmund JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter Am J Physiol Renal Physiol, October 1, 1999; 277(4): F634 - F642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Catanzaro, R. Chen, Y. Yan, L. Hu, J. E. Sealey, and J. H. Laragh Appropriate Regulation of Renin and Blood Pressure in 45-kb Human Renin/Human Angiotensinogen Transgenic Mice Hypertension, January 1, 1999; 33(1): 318 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yan, R. Chen, T. Pitarresi, C. D. Sigmund, K. W. Gross, J. E. Sealey, J. H. Laragh, and D. F. Catanzaro Kidney Is the Only Source of Human Plasma Renin in 45-kb Human Renin Transgenic Mice Circ. Res., December 14, 1998; 83(12): 1279 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Davisson, G. Yang, T. G. Beltz, M. D. Cassell, A. K. Johnson, and C. D. Sigmund The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes Circ. Res., November 16, 1998; 83(10): 1047 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yan, L. Hu, R. Chen, J. E. Sealey, J. H. Laragh, and D. F. Catanzaro Appropriate Regulation of Human Renin Gene Expression and Secretion in 45-kb Human Renin Transgenic Mice Hypertension, August 1, 1998; 32(2): 205 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Morimoto, M. D. Cassell, and C. D. Sigmund The Brain Renin-Angiotensin System in Transgenic Mice Carrying a Highly Regulated Human Renin Transgene Circ. Res., January 11, 2002; 90(1): 80 - 86. [Abstract] [Full Text] [PDF]
|
|