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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...

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Autores principales: Rafiq, Kazi, Sherajee, Shamshad J., Hitomi, Hirofumi, Nakano, Daisuke, Kobori, Hiroyuki, Ohmori, Koji, Mori, Hirohito, Kobara, Hideki, Masaki, Tsutomu, Kohno, Masakazu, Nishiyama, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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.
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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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