[Effects of docosahexaenoic acid on hypoxia-induced pulmonary arterial hypertension].

ABSTRACT

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on hypoxia-induced pulmonary arterial hypertension(PAH) and the mechanism. METHODS: PAH was induced by chronic intermittent hypoxia for 21 days in vivo. Forty male Sprague-Dawley rats were randomly divided into 4 groups (n = 10, each)a normal control group, DHA-treated groups in normoxia and hypoxia, and a PAH group. At the end of study, mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy and the index of wall thickness of small pulmonary artery (WT% and WA%) among groups were compared. The changes of pulmonary arterial smooth muscle cell (PASMC) proliferation were determined by MTT in vitro. Migration assay was performed using the Boyden chamber. Real-time quantitative PCR was performed to quantify mRNA levels of the smooth muscle cell phenotype markers SM-α-actin, calponin and SM 22α under normoxic or hypoxic conditions, in the absence or presence of DHA. RESULTS: DHA treatment significantly lowered mPAP [(22.7 ± 1.8) mmHg (1 mmHg = 0.133 kPa)], reduced thickening of small pulmonary artery wall [WT%(21.6 ± 4.1)%, WA% (52.0 ± 2.9)% ] and alleviated ventricular hypertrophy (34.2 ± 2.2) % compared to those of the hypoxic group (P < 0.05). DHA inhibited the proliferation, migration and phenotype switching of PASMCs induced by hypoxia in vitro. CONCLUSION: DHA therapy reduced mPAP in a rat model of hypoxia-induced PAH and this effect was linked with inhibition of pulmonary vascular remodelling.