Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension.
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.
Ishikura
Ken
K
Department of Cardiology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.
Yamada
Norikazu
N
Ito
Masaaki
M
Ota
Satoshi
S
Nakamura
Mashio
M
Isaka
Naoki
N
Nakano
Takeshi
T
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
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