Alleviation of hypoxic pulmonary vascular structural remodeling by L-arginine.
OBJECTIVE
To explore the effect of L-arginine on hypoxic pulmonary vascular structural remodeling and its possible mechanisms.


METHODS
Eighteen Wistar rats were randomly divided into three groups: the hypoxia group, the hypoxia with L-arginine group and the control group. Pulmonary artery mean pressure was evaluated with right cardiac catheterization. Pulmonary vascular structural changes were also observed. Plasma concentration of nitric oxide (NO) was measured via spectrophotometry, and endothelin-1 (ET-1) mRNA expression in pulmonary artery endothelial cells was detected using in situ hybridization.


RESULTS
The pulmonary artery mean pressure was significantly high in hypoxic rats than in normal controls (20.33 +/- 2.18 mm Hg vs 15.38 +/- 1.05 mm Hg, P < 0.05). Microstructural and ultrastructural analysis revealed the development of hypoxic pulmonary vascular structural remodeling in the hypoxic rats. Meanwhile, the plasma NO concentration was markedly lower in the hypoxic rats than in controls (P < 0.05). The expression signals of ET-1 mRNA by pulmonary artery endothelial cells of hypoxic rats strengthened obviously. L-arginine ameliorated pulmonary hypertension (16.73 +/- 1.35 mm Hg vs 20.33 +/- 2.18 mm Hg, P < 0.05) as well as pulmonary vascular structural remodeling in the hypoxic rats in association with an increase in plasma NO concentration (P < 0.05) and inhibited ET-1 mRNA expression by the endothelial cells of pulmonary arteries.


CONCLUSIONS
L-arginine might play an important role in the regulation of hypoxic pulmonary vascular structural remodeling and hypoxic pulmonary hypertension. The mechanism is probably related to promoting NO production and, as a result, inhibiting ET-1 mRNA expression by pulmonary artery endothelial cells in hypoxic rats.
Qi
J
J
Department of Pediatrics, First Hospital of Peking University, Beijing 100034, China.
Du
J
J
Wang
L
L
Zhao
B
B
Tang
C
C
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine