Role of Ca sensitivity in NO inhalation for pulmonary hypertension

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To determine if increased Ca sensitivity is observed in pulmonary hypertension, we measured pulmonary pressure in pulmonary hypertensive rats after administration of Rho-kinase inhibitor. As pulmonary hypertensive rats, two models were used : chronic hypoxic pulmonary hypertension and monocrotaline-induced pulmonaryhypertension. We used Y-27632 as Rho-kinase inhibitor which had been used to show increased Ca sensitivity in systemic hypertension. Y-27632 reduced pulmonary artery pressure in both model of pulmonary hypertension, while saline did not reduced pulmonary artery pressure. This results suggested that increased Ca sensitivity might be a part of pathogenesis of pulmonary hypertension. In addition, to determine if chronic administraction of Rho-kinase inhibitor might prevent the development of pulmonary hypertension and hypertensive pulmonary vascular changes, we gave Y-27632 to rats during 10days hypoxic exposure. Chronic administration of Y-27632 did not prevent the development of pulmonary hypertension and hypertensive pulmonary vascular changes. In terms of chronic effects of Rho-kinase inhibition on the development of pulmonary hypertension, we need to investigate another Rho-kinase inhibitor.