Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9–11 weeks) and aged (22–24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46±7% compared with 69±8%; aged, 52±5% compared with 80±3%; P<0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P<0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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February 2006
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Research Article|
January 17 2006
Endothelial dysfunction in growth hormone transgenic mice
Irene J. Andersson;
Irene J. Andersson
*Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Maria E. Johansson;
Maria E. Johansson
*Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Anna Wickman;
Anna Wickman
*Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Mohammad Bohlooly-Y;
Mohammad Bohlooly-Y
†AstraZeneca, AstraZeneca R&D, Mölndal, Sweden
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Natalia Klintland;
Natalia Klintland
‡Department of Clinical Physiology, The Cardiovascular Institute, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Kenneth Caidahl;
Kenneth Caidahl
‡Department of Clinical Physiology, The Cardiovascular Institute, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Maria Gustafsson;
Maria Gustafsson
§Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Jan Borén;
Jan Borén
§Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Li-ming Gan;
Li-ming Gan
*Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
‡Department of Clinical Physiology, The Cardiovascular Institute, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Göran Bergström
*Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
‡Department of Clinical Physiology, The Cardiovascular Institute, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Correspondence: Dr Göran Bergström, Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden (email goran.bergstrom@hjl.gu.se).
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Publisher: Portland Press Ltd
Received:
September 13 2005
Accepted:
September 27 2005
Accepted Manuscript online:
September 27 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2006
Clin Sci (Lond) (2006) 110 (2): 217–225.
Article history
Received:
September 13 2005
Accepted:
September 27 2005
Accepted Manuscript online:
September 27 2005
Citation
Irene J. Andersson, Maria E. Johansson, Anna Wickman, Mohammad Bohlooly-Y, Natalia Klintland, Kenneth Caidahl, Maria Gustafsson, Jan Borén, Li-ming Gan, Göran Bergström; Endothelial dysfunction in growth hormone transgenic mice. Clin Sci (Lond) 1 February 2006; 110 (2): 217–225. doi: https://doi.org/10.1042/CS20050281
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