Ghrelin Decreases Angiogenesis, HIF-1α and VEGF Protein Levels in Chronic Hypoxia in Lung Tissue of Male Rats.

PURPOSE: Hypoxia is a condition of decreased availability of oxygen. When cells are exposed to a low oxygen environment, they impel the hypoxia responses to adapt to new situation. The hypoxia response leads to the activation of various cellular signaling pathways. The aim of this study was to evaluate the effect of ghrelin on angiogenesis, Hypoxia-Inducible-Factor-1α (HIF-1) and Vascular endothelial growth factor (VEGF) levels in normobaric hypoxia situation. METHODS: Twenty four animals were divided into 4 groups (n=6): control (C), ghrelin (Gh), hypoxia (H), and hypoxic animals that received ghrelin (H+Gh). Hypoxia (11%) was induced by an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received a subcutaneous injection of ghrelin (150 µg/kg/day) for 14 days. RESULTS: Our results showed that hypoxia significantly (p<0.05) increased angiogenesis without any significant changes on HIF-1 and VEGF levels, whereas ghrelin significantly (p<0.05) decreased angiogenesis, expression of HIF-1 and VEGF in this condition. Ghrelin administration did not show any significant changes in normal conditions. CONCLUSION: Ghrelin had no effect on angiogenesis, expression of HIF-1 and VEGF in normal oxygen conditions but it reduced angiogenesis process in lung tissue with reducing the level of HIF and VEGF in hypoxic condition. Therefore, effect of ghrelin on angiogenesis could be related to blood oxygen level.

Ghrelin increases lymphocytes in chronic normobaric hypoxia.

PURPOSE: Hypoxia is a condition of decreased availability of oxygen. To adapt hypoxia, some changes in blood cells occur in the body. The aim of this study was to evaluate the effect of ghrelin on different types of blood cell in normobaric hypoxia situation. METHODS: Thirty-two animals were divided in 4 groups (n=8): control (C), ghrelin (G), hypoxia (H), and hypoxic animals that received ghrelin (H+G). Hypoxia (11%) was induced by an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received a subcutaneous injection of ghrelin (150 μg/kg/day) for 14 days. RESULTS: Our results show that ghrelin significantly (p<0.05) increased RBC and Hct levels, whereas it significantly (p<0.05) decreased lymphocytes in the blood. RBC, Hct, Hb concentration, platelet and MCV increased significantly (p<0.05) in hypoxic conditions but lymphocytes, monocytes and Polymorphonuclears did not show any significant changes. Platelets had a significant (p<0.05) decrease in hypoxic conditions and ghrelin administration in hypoxic conditions could increase lymphocyte levels significantly (p<0.05). CONCLUSION: Effect of ghrelin on blood cells could be related to blood oxygen level. Ghrelin in normal oxygen conditions increases RBC and Hct levels but decreases lymphocytes, whereas in hypoxic conditions, ghrelin increases blood lymphocytes.