摘要
Background Obstructive sleep apnea is a frequent medical condition consisting of repetitive sleep-related episodes of upper air ways obstruction and can lead to hypertension. Ang II type 1 receptor （AT1R） played important roles in hypertension since it binds with Ang II, controlling salt-water and blood pressure homeostasis. This study explores rat aorta AT1R expression during intermittent hypoxia （IH） and the signaling pathways involved. Methods A rat model and a cell model used a BioSpherix-OxyCycler A84 system and a ProOx C21 system respectively. The arterial blood pressure was recorded by a Nihon Kohden Polygraph System. Immunohistochemic was used to focus and analyze the expression of AT1R in rat aorta. Real-time PCR and Western blotting were used to explore the signaling pathways that participated in AT1R expression. Results In this study, we found that chronic intermittent hypoxia （CIH） induced AT1R transcription which increased the blood pressure in rat aorta compared to normoxia and to sustained hypoxia. The AT1R protein expression in the aorta was similar to the real-time PCR results. We explored the signaling mechanisms involved in the AT1R induction in both rat aorta and the aortic endothelial cells by real-time PCR and Western blotting. Compared to normoxia, CIH increased ERK1 mRNA transcription but not ERK2 or p38MAPK in the aorta; whereas sustained hypoxia （SH） upregulated ERK2 but not ERK1 or p38MAPK mRNA. In cells, IH induced AT1R expression with ERK1/2 phosphorylation but reduced p38MAPKs phosphorylation, whereas SH induced only ERK1/2 phosphorylation. The ERK1/2 inhibitor PD98059 attenuated the IH- induced AT1R increase but the p38MAPK inhibitor SB203580 did not. Conclusions Our results indicate that CIH induced the elevation of rat blood pressure and aorta AT1R expression. Moreover, ATIR expression in IH and sustained hypoxia might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.
Background Obstructive sleep apnea is a frequent medical condition consisting of repetitive sleep-related episodes of upper air ways obstruction and can lead to hypertension. Ang II type 1 receptor （AT1R） played important roles in hypertension since it binds with Ang II, controlling salt-water and blood pressure homeostasis. This study explores rat aorta AT1R expression during intermittent hypoxia （IH） and the signaling pathways involved. Methods A rat model and a cell model used a BioSpherix-OxyCycler A84 system and a ProOx C21 system respectively. The arterial blood pressure was recorded by a Nihon Kohden Polygraph System. Immunohistochemic was used to focus and analyze the expression of AT1R in rat aorta. Real-time PCR and Western blotting were used to explore the signaling pathways that participated in AT1R expression. Results In this study, we found that chronic intermittent hypoxia （CIH） induced AT1R transcription which increased the blood pressure in rat aorta compared to normoxia and to sustained hypoxia. The AT1R protein expression in the aorta was similar to the real-time PCR results. We explored the signaling mechanisms involved in the AT1R induction in both rat aorta and the aortic endothelial cells by real-time PCR and Western blotting. Compared to normoxia, CIH increased ERK1 mRNA transcription but not ERK2 or p38MAPK in the aorta; whereas sustained hypoxia （SH） upregulated ERK2 but not ERK1 or p38MAPK mRNA. In cells, IH induced AT1R expression with ERK1/2 phosphorylation but reduced p38MAPKs phosphorylation, whereas SH induced only ERK1/2 phosphorylation. The ERK1/2 inhibitor PD98059 attenuated the IH- induced AT1R increase but the p38MAPK inhibitor SB203580 did not. Conclusions Our results indicate that CIH induced the elevation of rat blood pressure and aorta AT1R expression. Moreover, ATIR expression in IH and sustained hypoxia might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.
基金
The research was supported by a grant from the National Natural Science Foundation of China （No. 81070067）. The authors decleard no conflict of interest.
