title: Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a poor prognostic disease with limited treatment options. Rho-kinase is involved in the pathophysiology of several diseases underlying smooth muscle hypercontraction, so the purpose of this study was to investigate the efficacy of fasudil, a Rho-kinase inhibitor, in patients with PAH.
  
  
  RESULTS
  Fasudil 30 mg was intravenously injected over 30 min in 8 patients (all female, mean +/- SD, 41+/-11 years) with PAH. The lowest total pulmonary resistance (TPR) time was within 30-60 min after administration. Administration of fasudil decreased TPR from 1,069+/-573 dyne . s . cm (-5) to 809+/-416 dyne . s . cm(-5) (p<0.005) and mean pulmonary arterial pressure from 41.3+/-12.8 mmHg to 37.9+/-14.6 mmHg (p<0.05). The cardiac index was increased from 2.42+/-0.73 L . min(-1) . m(-2) to 2.84+/-0.79 L . min(-1) . m(-2) (p<0.02). Systemic vascular resistance and systolic systemic arterial pressure (SAP) were decreased (p<0.005, p=0.09, respectively), but the decrease in SAP was small (-6.4+/-9.1 mmHg).
  
  
  CONCLUSIONS
  These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.
authors.affiliation: Department of Cardiology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishikura
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yamada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ota
authors.forename: Mashio
authors.initials: M
authors.lastname: Nakamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Isaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007275:Injections, Intravenous; D047908:Intracellular Signaling Peptides and Proteins; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054460:rho-Associated Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil