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Departments of 1 Circulation and 2 Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan 464-8601
The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K+ channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 ± 0.01 vs. 0.58 ± 0.03 ms (n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 ± 2.6 ms vs. 31.5 ± 5.8 ms (n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 ± 8.9 ms vs. 110.0 ± 4.2 ms (n = 6); P < 0.05] and corrected Q-T interval [Q-Tc; control vs. MCT: 8.4 ± 0.7 ms vs. 10.2 ± 0.4 ms (n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4.3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 ± 10, 76 ± 3, 58 ± 5, 81 ± 5, and 45 ± 12%, respectively (n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 ± 0.28 vs. 0.88 ± 0.44 (arbitrary units) (n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 ± 0.25 vs. 0.87 ± 0.18 (n = 3), NS; Kv1.4: 1.0 ± 0.22 vs. 1.27 ± 0.37 (n = 3), NS; Kv1.5: 1.0 ± 0.16 vs. 0.91 ± 0.28 (n = 3), NS; Kv2.1: 1.0 ± 0.26 vs. 0.99 ± 0.25 (n = 3), NS; Kv4.2: 1.0 ± 0.15 vs. 1.22 ± 0.28 (n = 3), NS; Kv4.3: 1.0 ± 0.20 vs. 1.21 ± 0.28 (n = 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K+ channels.
ventricular hypertrophy; voltage-gated potassium channels; messenger ribonucleic acid expression
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