The remodeling of connexin in the hypertrophied right ventricular in pulmonary arterial hypertension and the effect of a dual ET receptor antagonist (bosentan).

Studies on the role of connexins (Cxs) in the pathogenesis of right ventricular (RV) hypertrophy in pulmonary arterial hypertension (PAH) have not been reported to date. Therefore, we established a rat model of PAH induced by monocrotaline (MCT), and they were randomized to three groups: Control, MCT, and MCT+bosentan. Through electromicroscopy, in the control group, the gap junctions were long and frequent in intercalated disks, and short and rare at the sites of side-side cell junctions. In the MCT group, the opposite distribution was detected. In the MCT+bosentan group, the distribution of gap junctions was similar to that in the control group. Using immunoconfocal microscopy, most of the Cx43 staining was aggregated at the cell termini, and staining was weak at the sites of side-side cell junctions in the control group. However, the distribution of Cx43 was opposite in the MCT group. In the MCT+bosentan group, the result was similar to that in the control group. Therefore, perturbation of connexin distribution may be associated with RV hypertrophy. Improving the distribution of Cx43 in RV myocardium may be one of the mechanisms of a dual ET receptor antagonist partly reversing the RV hypertrophy.