Open AccessFTY 720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation
Author(s) -
Zhao Zhen,
Wang Jinxin,
Huo Zhijun,
Wang Zhiyong,
Mei Qibing
Publication year - 2017
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.308
Subject(s) - medicine , mapk/erk pathway , contractility , blood pressure , pharmacology , contraction (grammar) , endocrinology , kinase , chemistry , biochemistry
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 FTY 720 is protective for brain against ischemic conditions. However, whether and how FTY 720 can modulate vascular tone and blood pressure remains to be determined. We showed that FTY 720 (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 PD 98059 (10 μ mol/L), an inhibitor of ERK activation abrogated the aforementioned enhanced response by FTY 720. In parallel, FTY 720 (1 mg/kg) led to a modest elevation of blood pressure in rats, effects also being prevented by PD 98059. In contrast, FTY 720 decreased the high potassium‐induced contractile response in basilarartery preparations from rabbits, an effect blocked by PD 98059. Together, FTY 720‐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 FTY 720 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.