title: Hypoxic pulmonary vasoconstriction and vascular contractility in monocrotaline-induced pulmonary arterial hypertensive rats.
abstract: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high K+(40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-NG-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.
authors.affiliation: Department of Physiology, Department of Biomedical Sciences and Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Chung-Ang University Red Cross College of Nursing, Seoul 06974, Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Yoo
keywords: Hypoxia; Monocrotaline; Pulmonary arterial hypertension; Pulmonary artery; Vascular remodeling