Background
Abnormal sympathetic hyperactivity has been shown to lead to pulmonary arterial hypertension (PAH) deterioration. The
Conclusion
TCST can suppress pulmonary artery remodelling and right heart failure in MCT-induced PAH. The main mechanism may be that TCST decreases the NE concentrations in lung tissues, thereby preventing NE from promoting PASMC proliferation mediated by the ERK-1/2 signalling pathway.
Methods
Rats were randomly divided into four groups, including a control group, an MCT group, an MCT + sham group and an MCT + TCST group. After performing haemodynamic and echocardiographic measurements, the rats were sacrificed for the histological study, and the norepinephrine (NE) concentrations and protein expression level of tyrosine hydroxylase (TH) were evaluated. The protein expression levels of extracellular signal-regulated kinase (ERK)-1/2, proliferating cell nuclear antigen (PCNA), cyclin A2 and cyclin D1 in pulmonary artery vessels and pulmonary arterial smooth muscle cells (PASMCs) were determined.
Results
Compared with the MCT + sham group, TCST profoundly reduced the mean pulmonary arterial pressure (mPAP) (22.02 ± 4.03 mmHg vs. 31.71 ± 2.94 mmHg), right ventricular systolic pressure (RVSP) (35.21 ± 5.59 mmHg vs. 48.36 ± 5.44 mmHg), medial wall thickness (WT%) (22.48 ± 1.75% vs. 46.10 ± 3.16%), and right ventricular transverse diameter (RVTD) (3.78 ± 0.40 mm vs. 4.36 ± 0.29 mm) and increased the tricuspid annular plane systolic excursion (TAPSE) (2.00 ± 0.12 mm vs. 1.41 ± 0.24 mm) (all P < 0.05). The NE concentrations and protein expression levels of TH were increased in the PAH rats but significantly decreased after TCST. Furthermore, TCST reduced the increased protein expression of PCNA, cyclin A2 and cyclin D1 induced by MCT in vivo. We also found that NE promoted PASMC viability and activated the ERK-1/2 pathway. However, the abovementioned NE-induced changes could be suppressed by the specific ERK-1/2 inhibitor U0126.