The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule
Abstract
The purpose of this study was to evaluate the physiological significance of a tissue renin-angiotensin system in the proximal tubule of the kidney. To accomplish this, we produced mice that express human renin (hREN) under the control of the kidney androgen-regulated promoter (KAP), which is androgen responsive. One of the lines expressed the hREN transgene primarily in the kidney. Renal expression of the transgene was undetectable in females but could be induced by testosterone treatment. Because the renin-angiotensin system is species specific, we bred KAP2-hREN mice with the mice expressing human angiotensinogen under the same promoter (KAP-hAGT) to produce offspring that expressed both transgenes. We measured mean arterial blood pressure (MAP) in the carotid artery of double-transgenic and control mice using radiotelemetry. Double-transgenic female mice had a normal baseline MAP (116 ± 4 mmHg, n = 8), which increased by 15 mmHg after 2 wk of testosterone treatment, and returned to baseline after elimination of the testosterone pellet. The change in arterial pressure paralleled the change in plasma testosterone. There was no MAP change in testosterone-treated control littermates. We conclude that dual production of renin and angiotensinogen in the renal proximal tubule can result in a systemic increase in arterial pressure. These data support a role for a tissue-specific renin-angiotensin system in the renal proximal tubule that contributes to the regulation of systemic blood pressure.
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“Since Angiotensin-I is an intermediary peptide found most abundant as inactive form in blood (Lavoie et al., 2004), it is not surprising that we were able to detect the increased level of angiotensin I in blood as well as kidney where the cleavage of angiotensinogen takes place.”
From Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides (2016) · cites this paper as Lavoie et al., 2004
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Cited by
Seyrantepe, V., Hinek, A., Peng, J., Fedjaev, M., Ernest, S., Kadota, Y., Canuel, M., Itoh, K., Morales, C. R., Lavoie, J., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.733212 · Cited by 112
Self-citationLysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides
Timur, Z. K., Akyildiz Demir, S., & Seyrantepe, V. (2016) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2016.00068 · Cited by 38
Metadata
- Authors
- Lavoie, J. L., Lake-Bruse, K. D., & Sigmund, C. D.
- Affiliations
- Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2004-05
- Volume
- 286
- Issue
- 5
- Pages
- F965-F971
- ISSN
- 1931-857X
- 1522-1466
- Cited by
- 94
- References
- 49
- Language
- en
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