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Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats
OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923047/ https://www.ncbi.nlm.nih.gov/pubmed/24533142 http://dx.doi.org/10.1371/journal.pone.0088722 |
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author | Zhou, Wugang Hong, Mona Zhang, Ke Chen, Dongrui Han, Weiqing Shen, Weili Zhu, Dingliang Gao, Pingjin |
author_facet | Zhou, Wugang Hong, Mona Zhang, Ke Chen, Dongrui Han, Weiqing Shen, Weili Zhu, Dingliang Gao, Pingjin |
author_sort | Zhou, Wugang |
collection | PubMed |
description | OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. RESULTS: Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. CONCLUSIONS: Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. |
format | Online Article Text |
id | pubmed-3923047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39230472014-02-14 Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats Zhou, Wugang Hong, Mona Zhang, Ke Chen, Dongrui Han, Weiqing Shen, Weili Zhu, Dingliang Gao, Pingjin PLoS One Research Article OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. RESULTS: Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. CONCLUSIONS: Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. Public Library of Science 2014-02-12 /pmc/articles/PMC3923047/ /pubmed/24533142 http://dx.doi.org/10.1371/journal.pone.0088722 Text en © 2014 Zhou 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 Zhou, Wugang Hong, Mona Zhang, Ke Chen, Dongrui Han, Weiqing Shen, Weili Zhu, Dingliang Gao, Pingjin Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats |
title | Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats |
title_full | Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats |
title_fullStr | Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats |
title_full_unstemmed | Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats |
title_short | Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats |
title_sort | mechanisms of improved aortic stiffness by arotinolol in spontaneously hypertensive rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923047/ https://www.ncbi.nlm.nih.gov/pubmed/24533142 http://dx.doi.org/10.1371/journal.pone.0088722 |
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