Lipid metabolism under chronic hypoxia (CH) has not received equal attention as intermittent hypoxia (IH). To determine the CH-induced changes in plasma and liver, as well as the mRNA and protein expression of two key enzymes in the triglyceride and cholesterol biosynthesis pathways, SREBP-1 (HMG-CoA reductase) and SREBP-2 (SCD-1), we exposed adult male Wistar rats to CH (4600 m; n=15) for 30 days compared to normoxic rats (n=15). The CH rats exhibited weight loss (p<0.001), higher hematocrit (%), and higher hemoglobin (g/dL) (p<0.01). In the plasma of CH rats, total cholesterol and LDL-cholesterol increased at day 15. VLDL-cholesterol and triglycerides (p<0.01) greatly increased (35%), while HDL-cholesterol decreased (p<0.01). Triglycerides and VLDL-cholesterol remained elevated by 28% at day 30 (p<0.01). Hepatic triglycerides increased two-fold, while total cholesterol increased by 51% (p<0.001; p<0.05). Upregulation of SCD-1 mRNA and protein was observed in the CH rats (p<0.01); however, no differences were observed in HMG-CoA reductase mRNA or protein expression in both groups. In conclusion, CH, like IH, alters lipid profiles by increasing triglycerides in the plasma and liver and upregulating triglyceride biosynthesis without affecting the cholesterol biosynthetic pathway. Additional involved mechanisms require further study because of the importance of lipids in cardiovascular risk.

Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer.