title: Endothelial dysfunction in growth hormone transgenic mice.
abstract: 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.
authors.affiliation: Department of Physiology, Institute of Physiology and Pharmacology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Andersson
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Wickman
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.forename: Natalia
authors.initials: N
authors.lastname: Klintland
authors.forename: Kenneth
authors.initials: K
authors.lastname: Caidahl
authors.forename: Maria
authors.initials: M
authors.lastname: Gustafsson
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Gan
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000172:Acromegaly / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D001011:Aorta; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002339:Carotid Arteries; D018678:Cholinergic Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018384:Oxidative Stress; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018678:Cholinergic Agents; D013006:Growth Hormone; D000109:Acetylcholine