| First Author | Chevalier M | Year | 2014 |
| Journal | Cardiovasc Res | Volume | 103 |
| Issue | 4 | Pages | 597-606 |
| PubMed ID | 25016616 | Mgi Jnum | J:230133 |
| Mgi Id | MGI:5755551 | Doi | 10.1093/cvr/cvu166 |
| Citation | Chevalier M, et al. (2014) T-type calcium channels are involved in hypoxic pulmonary hypertension. Cardiovasc Res 103(4):597-606 |
| abstractText | AIMS: Pulmonary hypertension (PH) is the main disease of pulmonary circulation. Alteration in calcium homeostasis in pulmonary artery smooth muscle cells (PASMCs) is recognized as a key feature in PH. The present study was undertaken to investigate the involvement of T-type voltage-gated calcium channels (T-VGCCs) in the control of the pulmonary vascular tone and thereby in the development of PH. METHODS AND RESULTS: Experiments were conducted in animals (rats and mice) kept 3-4 weeks in either normal (normoxic) or hypoxic environment (hypobaric chamber) to induce chronic hypoxia (CH) PH. In vivo, chronic treatment of CH rats with the T-VGCC blocker, TTA-A2, prevented PH and the associated vascular hyperreactivity, pulmonary arterial remodelling, and right cardiac hypertrophy. Deletion of the Cav3.1 gene (a T-VGCC isoform) protected mice from CH-PH. In vitro, patch-clamp and PCR experiments revealed the presence of T-VGCCs (mainly Cav3.1 and Cav3.2) in PASMCs. Mibefradil, NNC550396, and TTA-A2 inhibited, in a concentration-dependent manner, T-VGCC current, KCl-induced contraction, and PASMC proliferation. CONCLUSION: The present study demonstrates that T-VGCCs contribute to intrapulmonary vascular reactivity and is implicated in the development of hypoxic PH. Specific blockers of T-VGCCs may thus prove useful for the therapeutic management of PH. |
