Changes and significance of endothelin-1 in lung tissue of hypoxic pulmonary hypertension development in neonatal rats

Abstract

Objective To know about the effect and significance of endothelin-1(ET-1)in pathogenesis of hypoxic pulmonary hypertension(HPH)in neonatal rats. Methods The 120 newborn Wistar rats were randomly divided into hypoxic group and control group, and the rats of hypoxic group were made into HPH model. Mean pulmonary arte-rial pressure(mPAP)was measured on day 3, 5, 7, 10, 14 and 21 after hypoxia. The morphological change of pulmonary vessels were observed, and pulmonary vascular remodeling indexes were also obtained, including the ratio of middle wall thickness to external diameter of small pulmonary arteries(MT%)and the ratio of media cross-section area to total cross-sectional area of small pulmonary arteries(MA%). Immunohistochemistry and Western blot tests were done to determine the expression of ET-1 in lung tissue. Results 1. After hypoxia for 3, 5, 7, 10, 14, 21 days, the levels of mPAP in hypoxia group[(8.492±1.548) mm Hg, (10.022±1.182) mm Hg, (11.470±2.868) mm Hg, (16.842±2.154) mm Hg, (12.824±2.859) mm Hg, (21.036±2.590) mm Hg; 1 mm Hg=0.133 kPa]were significantly higher than those in control group[(5.141±1.022) mm Hg, (8.137±1.057) mm Hg, (8.730±0.868) mm Hg, (12.125±2.541) mm Hg, (8.920±0.744) mm Hg, (11.156±1.644) mm Hg](all P 0.05). Conclusions The level of ET-1 in lung tissue of HPH newborn rats increased in the early stage after hypoxia exposure and no longer increased during the late stage, which indicated that hypoxia tolerance prevailed. ET-1 acted as an early reactive marker in the process of HPH development in neonatal rats and may be mainly associated with elevated mPAP, which further prompted that through valid means to inhibit the expression of ET-1 in the early stage of hypoxia, in which the prevention and treatment of this disease may be more effective. Key words: Hypoxic pulmonary hypertension; Endothelin-1; Vascular remodeling; Rat, neonatal