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Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice
Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858271/ https://www.ncbi.nlm.nih.gov/pubmed/24339994 http://dx.doi.org/10.1371/journal.pone.0082082 |
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author | Rafiq, Kazi Sherajee, Shamshad J. Hitomi, Hirofumi Nakano, Daisuke Kobori, Hiroyuki Ohmori, Koji Mori, Hirohito Kobara, Hideki Masaki, Tsutomu Kohno, Masakazu Nishiyama, Akira |
author_facet | Rafiq, Kazi Sherajee, Shamshad J. Hitomi, Hirofumi Nakano, Daisuke Kobori, Hiroyuki Ohmori, Koji Mori, Hirohito Kobara, Hideki Masaki, Tsutomu Kohno, Masakazu Nishiyama, Akira |
author_sort | Rafiq, Kazi |
collection | PubMed |
description | Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y) mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-A(y) mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes. |
format | Online Article Text |
id | pubmed-3858271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38582712013-12-11 Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice Rafiq, Kazi Sherajee, Shamshad J. Hitomi, Hirofumi Nakano, Daisuke Kobori, Hiroyuki Ohmori, Koji Mori, Hirohito Kobara, Hideki Masaki, Tsutomu Kohno, Masakazu Nishiyama, Akira PLoS One Research Article Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y) mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-A(y) mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes. Public Library of Science 2013-12-10 /pmc/articles/PMC3858271/ /pubmed/24339994 http://dx.doi.org/10.1371/journal.pone.0082082 Text en © 2013 Rafiq et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rafiq, Kazi Sherajee, Shamshad J. Hitomi, Hirofumi Nakano, Daisuke Kobori, Hiroyuki Ohmori, Koji Mori, Hirohito Kobara, Hideki Masaki, Tsutomu Kohno, Masakazu Nishiyama, Akira Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice |
title | Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice |
title_full | Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice |
title_fullStr | Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice |
title_full_unstemmed | Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice |
title_short | Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT(1) Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice |
title_sort | calcium channel blocker enhances beneficial effects of an angiotensin ii at(1) receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858271/ https://www.ncbi.nlm.nih.gov/pubmed/24339994 http://dx.doi.org/10.1371/journal.pone.0082082 |
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