Rho-kinase inhibitor decreased pulmonary artery resistance, whereas increased compliance in a rat model of pulmonary hypertension

Abstract

Although the dynamic mechanical properties such as arterial compliance (C) have been shown to predict increased mortality in patients with pulmonary arterial hypertension (PAH), a simple static index, i.e., pulmonary arterial resistance (R) has been exclusively used in clinical settings. We examined how a Rho-kinase inhibitor, fasudil, that is known to suppress vasoconstriction, affects pulmonary artery input impedance (Z) in Sugen/Hypoxia (SuHx) PAH in rats. We measured Z before PAH induction (Normal), and re-measured before/after fasudil injection (10 mg/kg) (PAH/Fasudil). PAH increased R while Fasudil decreased R (Normal: 16.3±2.6, PAH: 56.5±6.9, Fasudil: 39.9±5.2 mmHg/ml/sec, p<0.01). In contrast, PAH decreased C while Fasudil increased C (Normal: 3.6±0.6, PAH: 1.8±0.4, Fasudil: 2.5±0.8 ×103 ml/mmHg, p<0.01). We conclude that the pulmonary arterial impedance may serve as a new tool in analyzing vascular mechanics to assess the severity or the drug efficacy in PAH patients.