Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension

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Abstract
We have recently demonstrated that Rho-kinase is substantially involved in the pathogenesis of a wide range of cardiovascular disease.2, 3 Rho-kinase suppresses myosin phosphatase activity by phosphorylating the myosin binding subunit of the enzyme and thus augments vascular smooth muscle cell (VSMC) contraction at a given intracellular calcium concentration.4 Indeed, we have demonstrated that a Rho-kinase inhibitor, fasudil, suppresses abnormal hyperconstriction of forearm and coronary arteries in animals and humans.2, 3 Moreover, we have recently demonstrated that Rho-kinase inhibition increases eNOS expression and decreases inflammatory cell migration or anigiotensin II induced mRNA expression of monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1 in vivo and in vitro.3 Our in vivo study also indicated that long term oral treatment with fasudil notably ameliorates monocrotaline induced PH and pulmonary vascular lesions in rats.5 In the present study, we thus examined the acute vasodilatory effects of pulmonary circulation by intravenous administration of fasudil in patients with severe PH.