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

Zhen Zhao1, Jinxin Wang1, Zhijun Huo1

  • 1State Key Laboratory of New Drug & Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry Shanghai 200437 China.

Pharmacology Research & Perspectives
|May 9, 2017
PubMed

Insights

FTY720, a sphingosine 1-phosphate (S1P) mimetic, enhances aortic contractility and blood pressure in rats via extracellular signal-regulated kinase (ERK) activation. This mechanism may improve brain blood flow, aiding ischemic stroke treatment.

Area of Science:

  • Cardiovascular research
  • Neuroscience
  • Pharmacology

Background:

  • Sphingosine 1-phosphate (S1P) is a key signaling lipid in cardiovascular and cerebrovascular diseases.
  • FTY720, an S1P mimetic, demonstrates neuroprotective effects in ischemic conditions.
  • The impact of FTY720 on vascular tone and blood pressure requires elucidation.

Purpose of the Study:

  • To investigate the effects of FTY720 on vascular contractility in different arterial beds.
  • To determine the role of extracellular signal-regulated kinase (ERK) in FTY720-mediated vascular responses.
  • To assess the potential of FTY720 as an adjuvant therapy for ischemic stroke.

Main Methods:

  • Assessment of FTY720's effect on contractile responses in rat thoracic aorta and rabbit basilar artery preparations.
  • Measurement of blood pressure changes in rats following FTY720 administration.
  • Inhibition of ERK activation using PD98059 to elucidate the underlying signaling pathway.

Main Results:

  • FTY720 (1 mg/kg) potentiated high potassium- and phenylephrine-induced contractions in rat aortic rings.
  • FTY720 administration resulted in a modest increase in rat blood pressure.
  • These effects were abrogated by the ERK inhibitor PD98059.
  • Conversely, FTY720 attenuated high potassium-induced contractions in rabbit basilar arteries, an effect also blocked by PD98059.

Conclusions:

  • FTY720 enhances aortic contractility and elevates blood pressure through ERK activation.
  • FTY720 exhibits differential effects on vascular tone, attenuating basilar artery contractility.
  • These findings suggest FTY720's potential to improve cerebral blood flow and serve as an adjuvant in ischemic stroke treatment.
Keywords:
ERKPD98059S1Pphosphorylationstroke

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