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. Methods and 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). Conclusion These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.