Effect of diltiazem on heme oxygenase-1 and nitric oxide synthase in rats with pulmonary hypertension
- VernacularTitle:地尔硫对肺动脉高压大鼠血红素氧合酶1和一氧化氮合酶的影响
- Author:
Ying CHEN
;
Yingmao RUAN
;
Li LI
;
Yan CHU
;
Xiaomei ZHOU
;
Xinlin XU
;
Lianzhuang ZHNAG
;
Wenxue SI
;
Xiaohui LI
- Publication Type:Journal Article
- Keywords:
Anoxia;
Diltiazem;
Heme oxygenase (decyclizing);
Nitric oxide synthase;
Pulmonary artery
- From:
Chinese Journal of Pathophysiology
1989;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
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.
