Hypoxic pulmonary vasoconstriction and vascular contractility in monocrotaline-induced pulmonary arterial hypertensive rats.
10.4196/kjpp.2016.20.6.641
- Author:
Hae Jin KIM
1
;
Hae Young YOO
Author Information
1. Department of Physiology, Department of Biomedical Sciences and Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
- Publication Type:Original Article
- Keywords:
Hypoxia;
Monocrotaline;
Pulmonary arterial hypertension;
Pulmonary artery;
Vascular remodeling
- MeSH:
Angiotensins;
Animals;
Anoxia;
Arterial Pressure;
Endothelial Cells;
Eosine Yellowish-(YS);
Heart Ventricles;
Hematoxylin;
Hypertension;
Hypertrophy;
Lung;
Models, Animal;
Monocrotaline;
Nitric Oxide Synthase;
Pulmonary Artery;
Rats*;
Vascular Remodeling;
Vascular Resistance;
Vasoconstriction*;
Vasoconstrictor Agents
- From:The Korean Journal of Physiology and Pharmacology
2016;20(6):641-647
- CountryRepublic of Korea
- Language:English
-
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-N(G)-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.
