Tsantan Sumtang Alleviates Chronic Hypoxia-Induced Pulmonary Hypertension by Inhibiting Proliferation of Pulmonary Vascular Cells

Autor: Zhanqiang Li, Li Silin, Rili Ge, Shan-Shan Su, Nan Xingmei, Qilian He, Dianxiang Lu, Ma Ke
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Adenosine monophosphate
Male
Article Subject
Hypertension
Pulmonary
Prostaglandin
lcsh:Medicine
030204 cardiovascular system & hematology
Pharmacology
Pulmonary Artery
Vascular Remodeling
General Biochemistry
Genetics and Molecular Biology
Muscle hypertrophy
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Right ventricular hypertrophy
medicine.artery
medicine
Animals
Medicine
Tibetan Traditional
Hypoxia
Cell Proliferation
Plants
Medicinal
General Immunology and Microbiology
Hypertrophy
Right Ventricular
Inward-rectifier potassium ion channel
business.industry
lcsh:R
General Medicine
medicine.disease
Pulmonary hypertension
Rats
030104 developmental biology
chemistry
Pulmonary artery
Chronic Disease
medicine.symptom
business
Vasoconstriction
Research Article
Zdroj: BioMed Research International, Vol 2018 (2018)
BioMed Research International
ISSN: 2314-6133
DOI: 10.1155/2018/9504158
Popis: Hypoxia-induced pulmonary hypertension (HPH) is a severe condition associated with significant morbidity and mortality in people living at high altitude. Tsantan Sumtang, a traditional Tibetan medicine, has been routinely used for the treatment of cardiopyretic disease, as well as stenocardia. Interestingly, our previous research found that Tsantan Sumtang improved HPH in rats maintaining in a hypobaric chamber. We performed a series of experiments to test the indexes of vasoconstriction and vascular remodeling, the key pathophysiological characteristics of HPH. Our results showed that Tsantan Sumtang relaxed noradrenaline (NE)-precontracted rat pulmonary artery rings in a concentration-dependent manner in vitro. The PGI2-cAMP (prostaglandin I2-cyclic adenosine monophosphate) pathway, NO-cGMP (nitric oxide-cyclic guanosine monophosphate) pathway, and the opening of K+ channels (inward rectifier K+ channels, large conductance Ca2+-activated K+ channels, and voltage-dependent K+ channels) might play major roles in the vasorelaxation effect. In vivo, the administration of Tsantan Sumtang resulted in a substantial decrease in the rat mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index (RVHI). The reduction of thickness of small pulmonary arterial wall and the WT% (the ratio of the vascular wall thickness to the vascular diameter) were observed. The smooth muscle muscularization of the arterials was alleviated by Tsantan Sumtang treatment at the same time. Tsantan Sumtang also reduced remodeling of pulmonary arterioles by suppressing the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), cyclin D1, and cyclin-dependent kinase 4 (CDK4) through inhibition of p27Kip1 degradation. Therefore, Tsantan Sumtang could be applied as a preventative medication for HPH, which would be a new use for this traditional medicine.
Databáze: OpenAIRE
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