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Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning
Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less at...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436186/ https://www.ncbi.nlm.nih.gov/pubmed/30916484 http://dx.doi.org/10.14814/phy2.14010 |
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author | Willeman, Mari N. Chawla, Monica K. Zempare, Marc A. Biwer, Lauren A Hoang, Lan T. Uprety, Ajay R. Fitzhugh, Megan C. De Both, Matthew Coleman, Paul D. Trouard, Theodore P. Alexander, Gene E. Mitchell, Kenneth D. Barnes, Carol A. Hale, Taben M. Huentelman, Matthew |
author_facet | Willeman, Mari N. Chawla, Monica K. Zempare, Marc A. Biwer, Lauren A Hoang, Lan T. Uprety, Ajay R. Fitzhugh, Megan C. De Both, Matthew Coleman, Paul D. Trouard, Theodore P. Alexander, Gene E. Mitchell, Kenneth D. Barnes, Carol A. Hale, Taben M. Huentelman, Matthew |
author_sort | Willeman, Mari N. |
collection | PubMed |
description | Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1‐Ren2 xenobiotic‐inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans. Male, 15‐month‐old transgenic rats were fed 0.15% indole‐3‐carbinol (I3C) chow to slowly induce renin‐dependent hypertension over a 6‐week period. Systolic blood pressure significantly increased, eventually reaching 200 mmHg by the end of the study period. In contrast, transgenic rats fed a control diet without I3C did not show significant changes in blood pressure (145 mmHg at the end of study). Hypertension was associated with cardiac, aortic, and renal hypertrophy as well as increased collagen deposition in the left ventricle and kidney of the I3C‐treated rats. Additionally, rats with hypertension showed reduced savings from prior spatial memory training when tested on the hippocampus‐dependent Morris swim task. Motor and sensory functions were found to be unaffected by induction of hypertension. Taken together, these data indicate a profound effect of hypertension not only on the cardiovascular‐renal axis but also on brain systems critically important for learning and memory. Future use of this model and approach may empower a more accurate investigation of the influence of aging on the systems responsible for cardiovascular, renal, and neurological health. |
format | Online Article Text |
id | pubmed-6436186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64361862019-04-08 Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning Willeman, Mari N. Chawla, Monica K. Zempare, Marc A. Biwer, Lauren A Hoang, Lan T. Uprety, Ajay R. Fitzhugh, Megan C. De Both, Matthew Coleman, Paul D. Trouard, Theodore P. Alexander, Gene E. Mitchell, Kenneth D. Barnes, Carol A. Hale, Taben M. Huentelman, Matthew Physiol Rep Original Research Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1‐Ren2 xenobiotic‐inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans. Male, 15‐month‐old transgenic rats were fed 0.15% indole‐3‐carbinol (I3C) chow to slowly induce renin‐dependent hypertension over a 6‐week period. Systolic blood pressure significantly increased, eventually reaching 200 mmHg by the end of the study period. In contrast, transgenic rats fed a control diet without I3C did not show significant changes in blood pressure (145 mmHg at the end of study). Hypertension was associated with cardiac, aortic, and renal hypertrophy as well as increased collagen deposition in the left ventricle and kidney of the I3C‐treated rats. Additionally, rats with hypertension showed reduced savings from prior spatial memory training when tested on the hippocampus‐dependent Morris swim task. Motor and sensory functions were found to be unaffected by induction of hypertension. Taken together, these data indicate a profound effect of hypertension not only on the cardiovascular‐renal axis but also on brain systems critically important for learning and memory. Future use of this model and approach may empower a more accurate investigation of the influence of aging on the systems responsible for cardiovascular, renal, and neurological health. John Wiley and Sons Inc. 2019-03-27 /pmc/articles/PMC6436186/ /pubmed/30916484 http://dx.doi.org/10.14814/phy2.14010 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Willeman, Mari N. Chawla, Monica K. Zempare, Marc A. Biwer, Lauren A Hoang, Lan T. Uprety, Ajay R. Fitzhugh, Megan C. De Both, Matthew Coleman, Paul D. Trouard, Theodore P. Alexander, Gene E. Mitchell, Kenneth D. Barnes, Carol A. Hale, Taben M. Huentelman, Matthew Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning |
title | Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning |
title_full | Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning |
title_fullStr | Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning |
title_full_unstemmed | Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning |
title_short | Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning |
title_sort | gradual hypertension induction in middle‐aged cyp1a1‐ren2 transgenic rats produces significant impairments in spatial learning |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436186/ https://www.ncbi.nlm.nih.gov/pubmed/30916484 http://dx.doi.org/10.14814/phy2.14010 |
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