[The mechanism responsible for alleviation of hypoxic pulmonary vascular structural remodeling by L-arginine].

OBJECTIVE

To explore the mechanism of the therapeutic effect of L-arginine on hypoxic pulmonary vascular structural remodeling.

METHODS

Eighteen age- and body weight-matched Wistar rats were randomly divided into hypoxic group, hypoxic with L-arginine group or control group. Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra-acinar pulmonary muscularized arteries were observed. Meanwhile, indirect 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 with a cRNA probe for ET-1.

RESULTS

mPAP was significantly increased in hypoxic rats (2.71 kPa +/- 0.29 kPa) as compared with that of normal controls (2.05 kPa +/- 0.14 kPa) (P < 0.05). Microstructure and ultrastructure of pulmonary arteries changed obviously in hypoxic rats with the development of hypoxic pulmonary vascular structural remodeling. Meanwhile, indirect plasma NO concentration in hypoxic rats (3.54 micromol/L +/- 0.47 micromol/L) was markedly decreased compared with controls (4.79 micromol/L +/- 0.17 micromol/L) (P < 0.05). The expression of ET-1 mRNA of hypoxic rats strengthened obviously. However, mPAP was significantly decreased in hypoxic rats treated with L-arginine (2.23 kPa +/- 0.18 kPa) as compared with that of hypoxic rats (2.71 kPa +/- 0.29 kPa) (P < 0.05). L-arginine ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in indirect plasma NO concentration (P < 0.05) and an inhibited ET-1 mRNA expression.

CONCLUSION

L-arginine plays an important role in the regulation of development of hypoxic pulmonary vascular remodeling and hypoxic pulmonary hypertension, promoting NO production and inhibiting ET-1 mRNA expression in hypoxic rats.