title: Dietary manganese suppresses alpha1 adrenergic receptor-mediated vascular contraction.
abstract: We examined the effect of dietary manganese (Mn) on the vascular contractile machinery in rat thoracic aortas. Weanling male Sprague-Dawley rats were fed either an Mn-deficient (MnD), Mn-adequate (MnA) or Mn-supplemented (MnS) diet (<1, 10-15 and 45-50 ppm Mn, respectively). After 15 weeks on the diets the rats were sacrificed and 3-mm aortic rings were contracted in six cumulative doses of the alpha(1) adrenergic receptor agonist L-phenylephrine (l-Phe, 10(-8) to 3 x 10(-6) M) under 1.5-g preload and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximal force (F(max)) of contraction and relaxation, as well as the vessel sensitivity (pD(2)) were determined. Manganese deficiency, assessed by hepatic Mn content, significantly lowered the rate of animal growth. A two-way analysis of variance revealed that MnS animals developed lower F(max) when contracted with L-Phe compared with the MnD and MnA animals (P</=.001). Thus, dietary Mn at levels of 45-50 ppm affects the contractile machinery by reducing maximal vessel contraction to an alpha(1) adrenergic agonist. The observed pD(2) was significantly greater in the MnD group compared with the MnA and MnS animals (P</=.001). Thus, restriction of dietary Mn affects vascular sensitivity to the alpha(1) adrenergic receptor. Our results demonstrate for the first time that dietary Mn influences the receptor signaling pathways and contractile machinery of vascular smooth muscle cells in response to an alpha(1) adrenergic receptor.
authors.affiliation: Department of Food Science and Human Nutrition, College of Natural Sciences, Forestry and Agriculture, University of Maine, Orono, ME 04469, USA.
authors.forename: Anastasia Z
authors.initials: AZ
authors.lastname: Kalea
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Harris
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Klimis-Zacas
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D008099:Liver / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000008:administration & dosage* / Q000172:deficiency* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D008345:Manganese