Change of voltage - dependent potassium channel protein mRNA expression of pulmonary artery smooth muscle in rats with chronic thromboembolic pulmonary hypertension

Abstract

Objective To establish the rat model of chronic thromboembolic pulmonary hypertension (CTEPH) , and to investigate the effect of pulmonary artery ligation on voltage - dependent potassium channel protein Kv1.5 and Kv2.1 mRNA expressions in rat pulmonary artery smooth muscle, further to clarify the mechanism of the CTEPH occurrence and development. Methods CTEPH rat models were established by left pulmonary artery ligation (LPAL) in male SD rats, and randomly divided into 2- week normal control group, 2- week LPAL group, 2- week sham operation group, 5- week normal control group, 5-week LPAL group and 5-week sham operation group (n=5 each). Direct right heart manometry was used to determine the right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure(mPAP) in the 6 groups. The heart weight was measured to examine right ventricular hypertrophy index. HE staining was used to determine the changes of lung tissues and pulmonary vascular structures by measuring relative pulmonary artery medial thickness (PAMT) , and vessel wall area/total area (WA/TA). Real-time quantitative PCR was used to determine the Kv1.5 and Kv2.1 mRNA expressions in pulmonary artery smooth muscle. Results The RVSP, mPAP and right ventricular hypertrophy index in LPAL groups at 2 and 5 weeks were significantly increased compared with those in the normal control groups and sham operation groups (all P<0.05). The PAMT and WA/TA value in LPAL groups at 2 and 5 weeks were significantly increased compared with those in the normal control groups and sham operation groups (all P<0.05). Compared with the normal control groups and sham operation groups, significantly thicker distal pulmonary artery smooth muscle layer, vascular stenosis and pulmonary vascular remodeling were found in the LPAL groups at 2 and 5 weeks. Pulmonary artery ligation can reduce the relative expressions of Kv1.5 and Kv2.1 mRNA in distal pulmonary artery smooth muscle. At 2 and 5 weeks after ligation, the relative expressions of Kv1.5 and Kv2.1 mRNA in pulmonary artery smooth muscle were [(67.56±12.23)% and (55.98±6.84)%] and [(59.71±6.25)% and (49.07±3.51)%], respectively, which were lower than those in the contemporary normal control groups and sham operation groups (all P<0.05). Conclusion CTEPH rat model is successfully established by LPAL. LPAL may be involved in the occurrence and development of CTEPH by down-regulatingthe voltage-dependent potassium channel protein Kv1.5 and Kv2.1 mRNA expressions in rat pulmonary artery smooth muscle. Key words: Hypertension, pulmonary; Pulmonaryembolism; Potassiumchannels, voltage - gated; Pulmonary artery smooth muscle