Endothelial function in a mouse model of myeloperoxidase deficiency.
Myeloperoxidase (MPO) activity is suggested to reduce the function of vascular nitric oxide, thereby contributing to endothelial dysfunction, although data in rodents are inconclusive. We examined vascular contractile and relaxant responses in MPO-deficient (MPO(-/-)) and wild-type mice to investigate the role for myeloperoxidase in the development of endothelial dysfunction. Carotid and saphenous arteries were taken from 8-month-old mice and studied in a myograph. Responses of carotid arteries to phenylephrine, high potassium, or acetylcholine (Ach) were statistically not different from controls. Treatment with lipopolysaccharide (LPS; to enhance endothelial dysfunction) reduced responses to Ach in MPO(-/-) but did not affect responses in wild-type. In response to high concentrations of Ach, carotid arteries responded with transient contractions, which were not different between the groups and not affected by LPS treatment. Saphenous arteries from MPO(-/-) had smaller normalized diameters and developed less contractile force. Vessels from MPO(-/-) were less sensitive to Ach than controls. These data suggest that mature MPO-deficient mice do not show enhanced endothelial function compared to wild-type mice, even when provoked with LPS treatment. The EDHF response appears to be reduced in MPO deficiency.
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
Veronika
V
Golubinskaya
Department of Molecular Pharmacology, AstraZeneca R&D, Pepparedsleden 1, 431 83 Mölndal, Sweden.
Ulla
U
Brandt-Eliasson
Department of Molecular Pharmacology, AstraZeneca R&D, Pepparedsleden 1, 431 83 Mölndal, Sweden.
Li-Ming
LM
Gan
Department of Molecular Pharmacology, AstraZeneca R&D, Pepparedsleden 1, 431 83 Mölndal, Sweden.
Martin
M
Kjerrulf
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
Holger
0000-0003-2350-7157
H
Nilsson
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008661:Metabolism, Inborn Errors / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D008070:Lipopolysaccharides; D009195:Peroxidase; D000109:Acetylcholine