Fasudil improves the endothelial dysfunction in the aorta of spontaneously hypertensive rats

Panagiota Tsounapi, Motoaki Saito, Kazuyuki Kitatani, Fotios Dimitriadis, Fumiya Ohmasa, Shogo Shimizu, Yukako Kinoshita, Atsushi Takenaka, Keisuke Satoh

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We investigated the effects of fasudil, a Rho kinase inhibitor, in the endothelial dysfunction of aortas from spontaneously hypertensive rats (SHRs). SHRs were divided in three groups; intraperitoneally (i.p.) vehicle-treated SHRs (SHR), SHRs treated with fasudil 3 mg/kg i.p. (Fas3), and SHRs treated with fasudil 10 mg/kg i.p. (Fas10). Vehicle-treated Wistar rats were used as normo-tensive control group. After a six-week-treatment, blood pressure and heart rate were measured by the tail cuff method. Afterwards animals were sacrificed and aortas were examined in vitro by organ bath studies to evaluate the contraction and relaxation ability. Rho kinase activity, myosin light chain (MLC), phosphorylated MLC (phospho-MLC), eNOS, phospho-eNOS protein expression and eNOS mRNA levels were evaluated. SHR demonstrated a significant hypercontractility and impaired relaxation compared to the control. Fasudil 10 mg/kg significantly corrected the hypercontractility, restored the relaxation, and significantly decreased the mean arterial blood pressure, while no change observed in the systolic blood pressure. Rho kinase activity was significantly higher in the SHR, and was significantly inhibited by the high dose of fasudil. There was a slight up-regulation in the MLC, and phospho-MLC protein levels in the SHR. eNOS and phospho-eNOS protein levels were significantly lower in the SHR, and this abnormality was significantly normalized by fasudil treatment. No significant difference was observed in the eNOS gene expression. This study suggests that fasudil by inhibiting the Rho kinase activity normalizes the eNOS expression and phosphorylation and ameliorates the endothelial dysfunction induced by hypertension in the SHR model.

Original languageEnglish
Pages (from-to)182-189
Number of pages8
JournalEuropean Journal of Pharmacology
Volume691
Issue number1-3
DOIs
Publication statusPublished - 2012 Sep 15

Keywords

  • Aorta
  • Endothelial dysfunction
  • Fasudil
  • Rho kinase inhibition
  • SHR
  • eNOS

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Fasudil improves the endothelial dysfunction in the aorta of spontaneously hypertensive rats'. Together they form a unique fingerprint.

  • Cite this

    Tsounapi, P., Saito, M., Kitatani, K., Dimitriadis, F., Ohmasa, F., Shimizu, S., Kinoshita, Y., Takenaka, A., & Satoh, K. (2012). Fasudil improves the endothelial dysfunction in the aorta of spontaneously hypertensive rats. European Journal of Pharmacology, 691(1-3), 182-189. https://doi.org/10.1016/j.ejphar.2012.07.016