Hypoxia combined with a high-fat diet aggravates pulmonary vascular endothelial dysfunction in rats.

Objectives: Hypoxia and high-fat diet are independent risk factors for pulmonary vascular endothelial dysfunction (VED); however, their interactive effects are poorly understood. This study aimed to elucidate the effect and mechanism of hypoxia combined with a high-fat diet on the pulmonary arterial endothelial structure and function in rats.

Methods: Forty rats were randomly assigned to a normal diet and normoxia, a normal diet and hypoxia, a high-fat diet and normoxia, and a high-fat diet and hypoxia. Pulmonary morphology, pulmonary VED, and nitric oxide synthase (NOS) were evaluated.

Results: Compared to single factor, high-fat diet and hypoxia showed impaired vascular structure, reduced endothelium-dependent vasodilation, increased tissue factor, pulmonary NOS mRNA, peroxynitrite, and plasma malondialdehyde in rats. Hypoxic exposure also increased endothelial NOS (eNOS) and phosphorylated eNOS at threonine 495 in rats fed with a high-fat diet.

Conclusions: Hypoxia combined with a high-fat diet aggravates pulmonary VED in rats, which may be associated with eNOS and nitric oxide (NO) dysfunction.