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Conference Paper: Low frequency intermittent hypoxia reduces endothelium-dependent contraction in C57 mice with diet-induced obesity
Title | Low frequency intermittent hypoxia reduces endothelium-dependent contraction in C57 mice with diet-induced obesity |
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Authors | |
Issue Date | 2016 |
Publisher | Hong Kong Academy of Medicine Press. The Journal's web site is located at http://www.hkmj.org/ |
Citation | The 21st Medical Research Conference (MRC 2016), Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 16 January 2016. In Hong Kong Medical Journal, 2016, v. 22 n. 1 suppl., p. 33, abstract no. 47 How to Cite? |
Abstract | INTRODUCTION: Obstructive sleep apnoea (OSA) is associated with elevated systemic oxidative stress and inflammation, resulting in endothelial dysfunction. Obesity, a major risk factor for the development and severity of OSA, also modulates contractile and relaxing responses in the blood vessels. OBJECTIVE: To study the impact of intermittent hypoxia (IH), a hallmark feature of OSA, on endothelium-dependent contraction and relaxation in lean and obese mice. METHODS: Male C57BL/6N mice were fed with normal (Std) or high-fat high-cholesterol (HFHC) diet for 6 weeks before exposing to normoxia (Air) or chronic IH (IH) treatment (10 hypoxic events/hour [O2 10% at nadir; 6 h/d]) for 6 weeks. All mice were then sacrificed and endothelial function was assessed ex vivo, using the wire myograph device. Quiescent carotid arteries were used to evaluate endothelium-dependent contraction to acetylcholine, in the presence of L-nitro-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase). To investigate the role of oxidative stress in mediating the endothelium-dependent contraction, half of the carotid arterial rings were pre-incubated with apocynin, an inhibitor for superoxide-generating enzyme, NADPH oxidase, together with L-NAME, before acetylcholine-induced contraction. Pre-contracted aortae were used to assess the endothelium-dependent relaxation to acetylcholine. RESULTS: In the presence of L-NAME, cumulative addition of acetylcholine induced a basal level of endothelium-dependent contraction in carotid artery of Std+Air group. The contraction was significantly increased when the mice were fed with HFHC diet (HFHC+Air) in comparison to Std+Air group. However, treatment with apocynin significantly abolished the augmented response in HFHC+Air. After IH exposure, the HFHC-induced endothelium-dependent contraction was significantly reduced in comparison to HFHC+Air group. There was comparable level of endothelium-dependent contraction between Std+Air and Std+IH groups. On the contrary, treatment with HFHC diet, IH, or their combination did not affect the endothelium-dependent relaxation in aorta compared to Std+Air. CONCLUSION: The data suggest the involvement of superoxide in HFHC-induced endothelium-dependent contraction in carotid artery without affecting the endothelium-dependent relaxation in obese mice. The reduction of HFHC-induced endothelium–dependent contraction on low-frequency IH exposure suggests a defensive mechanism on endothelial function. |
Persistent Identifier | http://hdl.handle.net/10722/232403 |
ISSN | 2023 Impact Factor: 3.1 2023 SCImago Journal Rankings: 0.261 |
DC Field | Value | Language |
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dc.contributor.author | Lee, YKM | - |
dc.contributor.author | Mak, JCW | - |
dc.contributor.author | Ip, MSM | - |
dc.date.accessioned | 2016-09-20T05:29:45Z | - |
dc.date.available | 2016-09-20T05:29:45Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | The 21st Medical Research Conference (MRC 2016), Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 16 January 2016. In Hong Kong Medical Journal, 2016, v. 22 n. 1 suppl., p. 33, abstract no. 47 | - |
dc.identifier.issn | 1024-2708 | - |
dc.identifier.uri | http://hdl.handle.net/10722/232403 | - |
dc.description.abstract | INTRODUCTION: Obstructive sleep apnoea (OSA) is associated with elevated systemic oxidative stress and inflammation, resulting in endothelial dysfunction. Obesity, a major risk factor for the development and severity of OSA, also modulates contractile and relaxing responses in the blood vessels. OBJECTIVE: To study the impact of intermittent hypoxia (IH), a hallmark feature of OSA, on endothelium-dependent contraction and relaxation in lean and obese mice. METHODS: Male C57BL/6N mice were fed with normal (Std) or high-fat high-cholesterol (HFHC) diet for 6 weeks before exposing to normoxia (Air) or chronic IH (IH) treatment (10 hypoxic events/hour [O2 10% at nadir; 6 h/d]) for 6 weeks. All mice were then sacrificed and endothelial function was assessed ex vivo, using the wire myograph device. Quiescent carotid arteries were used to evaluate endothelium-dependent contraction to acetylcholine, in the presence of L-nitro-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase). To investigate the role of oxidative stress in mediating the endothelium-dependent contraction, half of the carotid arterial rings were pre-incubated with apocynin, an inhibitor for superoxide-generating enzyme, NADPH oxidase, together with L-NAME, before acetylcholine-induced contraction. Pre-contracted aortae were used to assess the endothelium-dependent relaxation to acetylcholine. RESULTS: In the presence of L-NAME, cumulative addition of acetylcholine induced a basal level of endothelium-dependent contraction in carotid artery of Std+Air group. The contraction was significantly increased when the mice were fed with HFHC diet (HFHC+Air) in comparison to Std+Air group. However, treatment with apocynin significantly abolished the augmented response in HFHC+Air. After IH exposure, the HFHC-induced endothelium-dependent contraction was significantly reduced in comparison to HFHC+Air group. There was comparable level of endothelium-dependent contraction between Std+Air and Std+IH groups. On the contrary, treatment with HFHC diet, IH, or their combination did not affect the endothelium-dependent relaxation in aorta compared to Std+Air. CONCLUSION: The data suggest the involvement of superoxide in HFHC-induced endothelium-dependent contraction in carotid artery without affecting the endothelium-dependent relaxation in obese mice. The reduction of HFHC-induced endothelium–dependent contraction on low-frequency IH exposure suggests a defensive mechanism on endothelial function. | - |
dc.language | eng | - |
dc.publisher | Hong Kong Academy of Medicine Press. The Journal's web site is located at http://www.hkmj.org/ | - |
dc.relation.ispartof | Hong Kong Medical Journal | - |
dc.rights | Hong Kong Medical Journal. Copyright © Hong Kong Academy of Medicine Press. | - |
dc.title | Low frequency intermittent hypoxia reduces endothelium-dependent contraction in C57 mice with diet-induced obesity | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Lee, YKM: leemary@hku.hk | - |
dc.identifier.email | Mak, JCW: judithmak@hku.hk | - |
dc.identifier.email | Ip, MSM: msmip@hku.hk | - |
dc.identifier.authority | Mak, JCW=rp00352 | - |
dc.identifier.authority | Ip, MSM=rp00347 | - |
dc.identifier.hkuros | 264107 | - |
dc.identifier.volume | 22 | - |
dc.identifier.issue | 1 suppl. | - |
dc.identifier.spage | 33, abstract no. 47 | - |
dc.identifier.epage | 33, abstract no. 47 | - |
dc.publisher.place | Hong Kong | - |
dc.identifier.issnl | 1024-2708 | - |