Effects of sodium tanshinone II A sulphonate on hypoxic pulmonary hypertension in rats in vivo and on Kv2.1 expression in pulmonary artery smooth muscle cells in vitro.
OBJECTIVE
To investigate the effect of sodium tanshinone IIA sulphonate (STS), a water-soluble derivative of tanshinone II A, on hypoxic pulmonary hypertension (HPH) in rats and its underlying mechanisms.


METHODS
Rats were exposed to hypoxia for two or three weeks, pretreated with or without STS. We detected mean pulmonary arterial pressure (mPAP), the ratio of right ventricle weight to left ventricle with septum weight [RV/(LV+S)], wall thickness and voltage-activated potassium channel (Kv) 2.1 mRNA level of pulmonary arteries (PAs), respectively, and the in vitro effects of STS on proliferation and Kv2.1 expression of cultured pulmonary smooth muscle cells (PASMCs) from normal rats. Cell proliferation was determined by 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazoliumbromiede (MTT) assay and direct cell counting. Kv2.1 mRNA and protein level were evaluated by reverse transcription-polymerase chain reaction and Western blot, respectively.


RESULTS
Chronic hypoxia increased values of mPAP and RV/(LV+S) and inhibited Kv2.1 mRNA level in PAs. Three weeks' daily STS pretreatment inhibited the hypoxia-induced increased mPAP and RV/(LV+S), pulmonary arterial thickening and up-regulated Kv2.1 mRNA level in PAs. Further study in vitro showed that STS suppressed significantly hypoxia-induced PASMCs proliferation and inhibition of Kv2.1 expression in PASMCs.


CONCLUSIONS
STS might play protective effects on HPH through decreasing mPAP, V/(LV+S) and inhibiting structural remodeling in distal PAs. The mechanism of these effects may be attributed to inhibiting PASMCs proliferation and stimulating Kv2.1 expression.
Huang
Yu-fang
YF
Department of Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China; Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
Liu
Man-ling
ML
Dong
Ming-qing
MQ
Yang
Wei-chuan
WC
Zhang
Bo
B
Luan
Li-li
LL
Dong
Hai-ying
HY
Xu
Min
M
Wang
Yan-xia
YX
Liu
Li-li
LL
Gao
Yu-Qi
YQ
Li
Zhi-chao
ZC
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels / Q000378:metabolism*
D010616:Phenanthrenes; D051669:Shab Potassium Channels; C024894:tanshinone II A sodium sulfonate