Capsaicin pretreatment reversed pulmonary arterial hypertension by alleviating inflammation via p38MAPK pathway

ABSTRACT

Purpose/Aim: Pulmonary arterial hypertension (PAH) is a lethal disease associated with pulmonary vascular remodeling as well as inflammation. As a kind of tachykinin secreted by nerves and inflammatory cells, substance P (SP) has been proved to be involved in the progression of PAH. Capsaicin can deplete substance P and provide benefits in PAH. However, the mechanism is still unclear. In this article, we aim to illustrate the possible mechanism involved in the process of capsaicin alleviating PAH. Materials and Methods: A single injection of monocrotaline (MCT) to male Sprague–Dawley (SD) rats was conducted to induce PAH. Capsaicin pretreatment was administered three days before MCT injection to deplete substance P. P38mitogen-activated protein kinase (p38MAPK) activator or inhibitor was given intraperitoneally after MCT injection. After 28 days, hemodynamic studies were carried out, and right ventricular systolic pressure (RVSP), right ventricular (RV)/left ventricle plus septum (LV+S), RV/body weight (BW), and lung weight (LW)/BW were recorded and calculated. In addition, the pulmonary vascular remodeling (pulmonary arterial medial wall thickness, area, perivascualr fibrosis), pro-inflammatory cytokines, the common signal pathways, such as peroxisome proliferator-activated receptor gamma (PPARγ), extracellular signal-regulated kinases (Erk), protein kinase B (Akt), and p38MAPK were also detected. Results: Capsaicin pretreatment reversed PAH, including decreasing RVSP, RV/(LV+S), RV/BW, and LW/BW, and alleviating inflammation. Phosphorylated-p38 (p-p38) MAPK was up-regulated, which was partially reversed by capsaicin pretreatment. Interestingly, expression of Akt, Erk, and PPARγ was not altered by capsaicin pretreatment. Inhibition of p38MAPK provided the same benefits with capsaicin pretreatment, whereas it failed to provide additional improvement in the presence of capsaicin. Besides, p38MAPK activator abolished the effects of capsaicin pretreatment on PAH, suggesting a key role of p38MPAK pathway in the effects of capsaicin reversing PAH. Conclusions: Capsaicin pretreatment reversed PAH by alleviating inflammation via p38MAPK pathway.

KEYWORDS:

• capsaicin
• substance P
• pulmonary arterial hypertension
• inflammation
• p38MAPK

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This work was supported by the project of National Natural Science Foundation of China [No. 81501202] and Natural science fund for colleges and universities in Jiangsu Province [16KJD320003] and Young Talent Program in Jiangsu Province [QNRC2016666].