Effects and mechanism of oridonin on pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.
- Author:
Liang-Xing WANG
1
;
Yu SUN
;
Chan CHEN
;
Xiao-Ying HUANG
;
Quan LIN
;
Guo-Qing QIAN
;
Wei DONG
;
Yan-Fan CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antihypertensive Agents; pharmacology; Apoptosis; Blotting, Western; Diterpenes, Kaurane; pharmacology; Hypercapnia; physiopathology; Hypertension, Pulmonary; drug therapy; Hypoxia; physiopathology; Immunohistochemistry; Male; Membrane Potential, Mitochondrial; Microscopy; Microscopy, Electron, Transmission; Pulmonary Artery; drug effects; Random Allocation; Rats; Rats, Sprague-Dawley
- From: Chinese Medical Journal 2009;122(12):1380-1387
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDPulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC.
METHODSThirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected.
RESULTSThe mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05).
CONCLUSIONSThe results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.
