AIM: To investigate the action of diltiazem (a calcium antagonist) on the expression of heme oxygenase (HO) -1 and nitric oxide synthase (NOS) in the small pulmonary arteries (SPA) of rat in chronic hypoxia. METHODS: Chronic pulmonary arterial hypertension models were established by treating the rats in hypoxic environment[(10%?1%)O 2] for 6 weeks. After 2 weeks of hypoxia, rats were treated with diltiazem (15 mg/kg/day). Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were measured. Pathological changes in the lungs were observed under the light microscope and transmission electron microscope. The expression and distribution of heme oxygenase (HO) -1, endothelial NOS (eNOS) and inducible NOS (iNOS) were tested by immunohistochemistry and Western blot. Guanosine-3', 5'-cyclic monophosphate (cGMP) of lung tissues were detected with radioimmunoassay. RESULTS: Diltiazem significantly decreased abnormal RVSP, and RVHI in model rats, attenuated the SPA media thickeness, and recovered abnormal eNOS and iNOS expression in SPA. Whereas diltiazem had little effect on the increased HO-1 expression in SPA caused by hypoxia and ultrastructure injury in endothelium. cGMP levels were corresponded with HO-1. CONCLUSION: Diltiazem has a significant effect on inhibiting hypoxic pulmonary hypertension structural remodeling. These effects might be partly attributed to the suppression of iNOS, promotion of eNOS, and not attenuation HO-1 expression in the lung of hypoxic rats.

Objective To observe the inhibitory effects of Radix Astragali (RA) on hypoxic structural remodeling of intraacinar pulmonary arteries (IAPA) and pulmonary hypertension (PHT).Methods　Sixty rats were divided into three groups: hypoxia group, hypoxia + RA group and normal control group. The rats of hypoxia group and hypoxia+RA group were fed in hypoxic environment under normal atmospheric pressure (10% O2, 10 h/day). On the 15 th and 30 th day of hypoxia, right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI) were measured and pulmonary vessel changes were studied under light and electron microscope and with morphometric analysis.Results　Compared with the result of hypoxia+RA group, RA could relieve IAPA wall cell injuries and dilate the constricted IAPA induced by hypoxia . RA could also inhibit hypertrophic changes in the tunica media and proliferation of adventitial cells of the IAPA and muscularization of nonmuscular arteries.Conclusion　By preserving the IAPA wall cells and dilating IAPA, RA may play an important role in inhibiting the remodeling of IAPA and preventing PHT.