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FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation

Sphingosine 1‐phosphate (S1P) is an important signaling sphingolipid involved in the pathogenesis of various cardio cerebral vascular diseases such as ischemic stroke. In particular, the S1P mimetic FTY720 is protective for brain against ischemic conditions. However, whether and how FTY720 can modul...

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Autores principales: Zhao, Zhen, Wang, Jinxin, Huo, Zhijun, Wang, Zhiyong, Mei, Qibing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415948/
https://www.ncbi.nlm.nih.gov/pubmed/28480040
http://dx.doi.org/10.1002/prp2.308
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author Zhao, Zhen
Wang, Jinxin
Huo, Zhijun
Wang, Zhiyong
Mei, Qibing
author_facet Zhao, Zhen
Wang, Jinxin
Huo, Zhijun
Wang, Zhiyong
Mei, Qibing
author_sort Zhao, Zhen
collection PubMed
description Sphingosine 1‐phosphate (S1P) is an important signaling sphingolipid involved in the pathogenesis of various cardio cerebral vascular diseases such as ischemic stroke. In particular, the S1P mimetic FTY720 is protective for brain against ischemic conditions. However, whether and how FTY720 can modulate vascular tone and blood pressure remains to be determined. We showed that FTY720 (1 mg/kg) enhanced the contractile response of rat thoracic aortic rings induced by high potassium and phenylephrine, respectively. This enhancement involves the activation of extracellular signal‐regulated kinase (ERK) since ERK phosphorylation was also enhanced and application of PD98059 (10 μmol/L), an inhibitor of ERK activation abrogated the aforementioned enhanced response by FTY720. In parallel, FTY720 (1 mg/kg) led to a modest elevation of blood pressure in rats, effects also being prevented by PD98059. In contrast, FTY720 decreased the high potassium‐induced contractile response in basilarartery preparations from rabbits, an effect blocked by PD98059. Together, FTY720‐induced an enhanced response of artery contractility in aorta and in arterial pressure involving ERK activation, with an attenuation in basilarartery contractility. This action property of FTY720 would be endowed with a potential of facilitating more blood flow perfusion to the brain and improving blood supply to the ischemic brain region and could be useful as an adjuvant in the treatment of ischemic stroke in the clinics.
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spelling pubmed-54159482017-05-05 FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation Zhao, Zhen Wang, Jinxin Huo, Zhijun Wang, Zhiyong Mei, Qibing Pharmacol Res Perspect Original Articles Sphingosine 1‐phosphate (S1P) is an important signaling sphingolipid involved in the pathogenesis of various cardio cerebral vascular diseases such as ischemic stroke. In particular, the S1P mimetic FTY720 is protective for brain against ischemic conditions. However, whether and how FTY720 can modulate vascular tone and blood pressure remains to be determined. We showed that FTY720 (1 mg/kg) enhanced the contractile response of rat thoracic aortic rings induced by high potassium and phenylephrine, respectively. This enhancement involves the activation of extracellular signal‐regulated kinase (ERK) since ERK phosphorylation was also enhanced and application of PD98059 (10 μmol/L), an inhibitor of ERK activation abrogated the aforementioned enhanced response by FTY720. In parallel, FTY720 (1 mg/kg) led to a modest elevation of blood pressure in rats, effects also being prevented by PD98059. In contrast, FTY720 decreased the high potassium‐induced contractile response in basilarartery preparations from rabbits, an effect blocked by PD98059. Together, FTY720‐induced an enhanced response of artery contractility in aorta and in arterial pressure involving ERK activation, with an attenuation in basilarartery contractility. This action property of FTY720 would be endowed with a potential of facilitating more blood flow perfusion to the brain and improving blood supply to the ischemic brain region and could be useful as an adjuvant in the treatment of ischemic stroke in the clinics. John Wiley and Sons Inc. 2017-04-17 /pmc/articles/PMC5415948/ /pubmed/28480040 http://dx.doi.org/10.1002/prp2.308 Text en © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the Creative Commons Attribution (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 Articles
Zhao, Zhen
Wang, Jinxin
Huo, Zhijun
Wang, Zhiyong
Mei, Qibing
FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
title FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
title_full FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
title_fullStr FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
title_full_unstemmed FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
title_short FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
title_sort fty720 elevates smooth muscle contraction of aorta and blood pressure in rats via erk activation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415948/
https://www.ncbi.nlm.nih.gov/pubmed/28480040
http://dx.doi.org/10.1002/prp2.308
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