title: Lessons from the adrenomedullin knockout mouse.
abstract: Because vasolidator peptide adrenomedullin (AM) exhibits complicated action, we developed AM knockout mice in order to elucidate the physiological and pathophysiological role of AM. The AM(-/-) mice were embryonic lethal, so we could not evaluate directly the role of AM in this mutant mice. Thus, we loaded angiotensin II (AngII) and salt in AM(+/-) mice, which were viable and fertile. As a result, AngII and salt loading caused coronary vascular damage and left ventricular hypertrophy in AM(+/-) mice more greatly than AM(+/+) mice. Moreover, cuff placement of femoral artery stimulated intimal thickening more severely. This treatment increased local AM levels in AM(+/+) mice but not in AM(+/-) mice. The accelerated organ damage in AM(+/-) mice was accompanied with enhanced production of oxidative stress. Thus, our data suggest that intrinsic AM play a vascular protective role.
authors.affiliation: Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Tokyo 113-8655, Bunkyoku, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D053607:Adrenomedullin; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018384:Oxidative Stress; D010455:Peptides / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism
chemical_list: D010455:Peptides; D000804:Angiotensin II; D053607:Adrenomedullin