Nicorandil improves the histopathological findings of MCT-injured lungs.

<p>(<b>A</b>) Immunohistochemical staining for αSMA (<b>a</b>), CD68 (<b>b</b>), and eNOS (<b>c</b>) in lung sections are shown. Histopathologically, MCT injury induced the thickened medial wall of PAs (arrows) that was composed of αSMA-positive cells, the recruitment of CD68-positive macrophages into the perivascular areas, and the deficiency of eNOS expression in the endothelium of the pulmonary vasculature (<i>see</i> vehicle). Nicorandil and ZVAD-fmk improved these deleterious histopathological changes in the MCT-injured lungs, whereas glibenclamide and l-NAME blocked the effects of nicorandil. Scale bar, 50 µm. (<b>B</b>) MCT readily induced thromboemboli formation that occluded the small PAs (arrows; <i>see</i> vehicle), which was attenuated by nicorandil. HE staining. Scale bars, 100 µm (top) and 50 µm (bottom). (<b>C</b>) The number of small PAs that were occluded by thromboemboli was counted in the lung sections. (<b>D</b>) TUNEL staining with immunofluorescence staining for αSMA in lung sections. MCT readily induced endothelial cell apoptosis (arrowheads) in a number of PAs (arrows; <i>see</i> vehicle), which was attenuated by nicorandil. TUNEL (green); αSMA (red); and nuclei (blue). Scale bars, 100 µm (top) and 20 µm (bottom). (<b>E</b>) The number of small PAs having TUNEL-positive endothelial cell(s) [EC(s)] was counted in lung sections, and the proportion of PAs with TUNEL-positive EC(s) in a total of equally sized PAs was calculated. ^#<i>P</i><0.01 vs. normal control; <b>^*</b><i>P</i><0.05 and <b>^**</b><i>P</i><0.01 vs. vehicle; <b>^†</b><i>P</i><0.05 and <b>^‡</b><i>P</i><0.01 vs. nicorandil (5.0 mg·kg⁻¹·day⁻¹).