Rho-kinase inhibitors show promise in pulmonary hypertension

In pulmonary arterial hypertension, it is necessary to obtain a vasodilation that is selective for the pulmonary circulation. Ras human orthologue (Rho)/Rho-kinase-mediated Ca2+ sensitisation plays a central role in mediating the sustained vasoconstriction and increased vasoreactivity in the rat hypoxic model of pulmonary hypertension. Rho-kinase inhibitors (Y-27632 and/or fasudil) have been shown to reduce pulmonary arterial pressure in three rat models of pulmonary hypertension. The first clinical study to report the effects of a Rho-kinase inhibitor in pulmonary hypertension enrolled nine patients with severe pulmonary hypertension. Fasudil hydrochloride 30 mg for 30 min i.v. caused a slight decrease in the mean pulmonary artery pressure and increase in the cardiac index but neither of these responses was significant. However, fasudil caused a significant decrease in pulmonary vascular resistance. Rho-kinase inhibitors may be useful in pulmonary hypertension, and should undergo further development for this indication.