OBJECTIVETo investigate the changes of endoplasmic reticulum stress-induced apoptosis in pulmonary tissue of rats with hypoxic pulmonary hypertension.

METHODSTwenty two male SD rats were randomly divided into control group and 4-week hypoxia-hypercapnia group (n=11). The mean pulmonary arterial pressure (mPAP) and the mean carotid arterial pressure (mCAP) were monitored, and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) were measured. The rattish pathological model were assessed by mPAP, mCAP, RV/(LV+ S), vessel wall area/total area (WA/TA), vessel cavity area/total area (CA/TA) and media thickness of pulmonary arteriole (PAMT). The pulmonary apoptotic cells were detected by Hoechst staining. RT-PCR was used to study the genetic expression of caspasel2, glucose regulated protein 78 (GRP78) and GRP94 in pulmonary tissue. The expression of GRP94 and GRP78 proteins in pulmonary tissue were determined by using immunohistochemistry.

RESULTS(1) (The mPAP, RV/(LV + S), WA/TA and PAMT were respectively higher by 50.5%, 37.3%, 72.5% and 137% in hypoxic group than those in control group, while CA/TA was lower by 41.9% (all P < 0.01). There was not significant difference of mCAP between the two groups. (2) Hoechst staining showed that the pulmonary apoptotic cells in hypoxic group outnumbered markedly than those in control group, and the apoptotic cells were mainly in pulmonary tissue, while they were rare in pulmonary vascular smooth muscle cell. (3) Compared with control group, the expression of pulmonary caspasel2, GRP78 and GRP94 mRNA in hypoxic group were higher by 144%, 137% and 80.7% (all P < 0.05), respectively. (4) The expression of pulmonary GRP78 and GRP94 proteins were up-regulated in hypoxic group, and these proteins mainly localized in pulmonary vascular endothelial cell.

CONCLUSIONThe endoplasmic reticulum stress-induced apoptosis may be one of the mechanism of hypoxic pulmonary hypertension and pulmonary vascular wall remodeling.