Impact of nitric oxide on platelet-derived growth factor expression in pulmonary arteries of rats with hypoxic pulmonary vascular remodeling

Abstract

Objective The pathological basis of chronically hypoxic pulmonary hypertension is pulmonary vascular structural remodeling. Nitric oxide (NO) , a new typical messenger of gas molecule, plays an important role in regulating hypoxic pulmonary vascular remodeling. However, the regulatory mechanism is unknown. Our present experiment aimed at examining the impact of NO on platelet-derived growth factor-B ( PDGF-B) expression in intrapulmonary arteries of rats with hypoxic pulmonary vascular remodeling, and thereby to investigate the role of PDGF in the mechanisms by which NO regulates hypoxic pulmonary vascular remodeling. Methods Twenty-five rats were randomly divided into four groups: normoxic group (n = 6) , hypoxic group (n = 6) , hypoxic + L-arginine group (hypoxic + L-Arg group, n = 7) and hypoxic + Nw-L-nitro-arginine methyl ester group (hypoxic+ L-NAME group, n = 6) . Relative medial thickness (RMT) of small and median muscularized pulmonary arteries was observed in lung sections of rats by using a light microscope. An immunohistochemical technique was used to assess the abundance and localization of PDGF in pulmonary arteries of rats in four groups. Results RMT of small and median intrapulmonary arteries in rats of hypoxic group was markedly higher than that of normoxic group and hypoxic + L-Arg group (P < 0.01) . Whereas RMT of small and median intrapulmonary arteries in rats of hypoxic + L-NAME group was obviously higher than that of hypoxic group (P < 0.01) . PDGF-B was expressed by pulmonary artery endothelial cells and smooth muscle cells in rats of 4 groups. In rats of nomioxic group, hypoxic group, hypoxic + L-Arg group and hypoxic + L-NAME group, PDGF expression score was 35.0,58.3,42.1 and 75.8, respectively, in endothelial cells of median pulmonary arteries, and 31.7,50.8,38.6 and 73.3, respectively in smooth muscle cells of median pulmonary arteries. The score was 38.3,57.5,47.1 and 78.3respectively, in endothelial cells of small pulmonary arteries, and 37.5 , 60.8 , 45.7 and 80.8, respectively, in smooth muscle cells of small pulmonary arteries. There was a positive correlation between RMT and PDGF expression by endothelial cells and smooth muscle cells of median pulmonary arteries (r = 0.8636,0.8264, P <0.01,respectively). There was also a positive correlation between RMT and PDGF expression by endothelial cells and smooth muscle cells of small pulmonary arteries (r = 0.8898,0.8688, P < 0.01, respectively) . Conclusion Nitric oxide inhibited PDGF expression by pulmonary arteries of rats with hypoxic pulmonary vascular remodeling. Key words: Nitric oxide; Platelet-derived growth factor; Anoxia; Pulmonary artery