Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension

Hiroshi Fujita, Yoshihiro Fukumoto, Kenya Saji, Koichiro Sugimura, Jun Demachi, Jun Nawata, Hiroaki Shimokawa

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, as a more feasible option to locally deliver the drug for PAH. We examined 15 patients with PAH (13 women and 2 men, 45 ± 4 years old), including idiopathic PAH (n = 5), PAH associated with connective tissue disease (n = 6), PAH with congenital heart disease (n = 3), and portal PAH (n = 1). In those patients, we performed right heart catheterization with a Swan-Ganz catheter in the two protocols with inhalation of nitric oxide (NO) (40 ppm, 10 min) and fasudil (30 mg, 10 min) with a sufficient interval (>30 min). Both NO and fasudil inhalation significantly reduced mean pulmonary arterial pressure (PAP) (NO: P < 0.01, fasudil: P < 0.05) and tended to decrease pulmonary vascular resistance (NO: P = 0.07, fasudil: P = 0.1), but did not affect cardiac index. The ratio of pulmonary to systemic vascular resistance was significantly reduced both in NO and fasudil inhalation (NO: P < 0.01, fasudil: P < 0.05), indicating that both NO and fasudil inhalation selectively affect lung tissues. Interestingly, there was no correlation in the vasodilator effects between NO and fasudil, and a positive correlation with serum levels of high-sensitivity C-reactive protein was noted for fasudil but not for NO. These results suggest that inhalation of fasudil is as effective as NO in patients with PAH, possibly through different mechanisms.

Original languageEnglish
Pages (from-to)144-149
Number of pages6
JournalHeart and Vessels
Volume25
Issue number2
DOIs
Publication statusPublished - 2010 Mar 1

Keywords

  • Inhalation
  • Pulmonary arterial hypertension
  • Pulmonary arterial pressure
  • Pulmonary vascular resistance
  • Rho-kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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