© 2000 American Heart Association, Inc.
Integrative Physiology |
Remodeling of Gap Junctional Coupling in Hypertrophied Right Ventricles of Rats With Monocrotaline-Induced Pulmonary Hypertension
From the Department of Circulation (M.U., I.K.), the Department of Humoral Regulation (H.H.), and the Department of Teratology and Genetics (Y.T., L.E.), Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; Laboratory of Eukaryotic Molecular Genetics (A.I.M.), National Institute for Medical Research, London, UK; and Department of Cardiac Medicine (N.J.S.), National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Correspondence to Haruo Honjo, Department of Humoral Regulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan. E-mail honjo{at}riem.nagoya-u.ac.jp
Abstract—The present study investigates the remodeling of gap junctional organization in relation to changes in anisotropic conduction properties in hypertrophied right ventricles (RVs) of rats with monocrotaline (MCT)-induced pulmonary hypertension. In contrast to controls that showed immunolocalization of connexin43 (Cx43) labeling largely confined to the intercalated disks, RV myocytes from MCT-treated rats showed dispersion of Cx43 labeling over the entire cell surface. The disorganization of Cx43 labeling became more pronounced with the progression of hypertrophy. Desmoplakin remained localized to the intercalated disks, as in controls. In RV tissues, the proportion of Cx43 label at the intercalated disk progressively decreased. Quantitative analysis of en face views of intercalated disks revealed a significant decrease in the disk gap junctional density in RV tissues of MCT-treated rats (control, 0.18 versus MCT-treated, 0.14 at 2 weeks; control, 0.16 versus MCT-treated, 0.11 at 4 weeks). Conduction velocity in RVs parallel to the fiber orientation was significantly lower (30.2% [n=9]) in MCT-treated rats at 4 weeks than in control rats, whereas there was no significant difference observed in the conduction velocity across the fiber orientation between control and MCT-treated rats. The anisotropic ratio of MCT-treated rats (1.38±0.10) was significantly lower than that of control rats (1.98±0.12). These results suggest that RV hypertrophy induced by pressure overload is associated with both disorganization of gap junction distribution and alteration of anisotropic conduction properties.
Key Words: ventricular hypertrophy • connexin • immunohistochemistry • anisotropy • conduction
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