title: Cyclo-oxygenase inhibition restores the attenuated vasodilation in manganese-deficient rat aorta.
abstract: Previously we showed that manganese (Mn) deficiency enhances the arterial contractile response to alpha(1) adrenergic stimuli and affects vasomotor tone. The aim of this study was to test the hypothesis that dietary Mn deficiency inhibits the vasodilation pathways of rat aorta. Vascular ring studies were conducted in aortic rings from weanling male Sprague-Dawley rats that were fed either a Mn deficient (MnD) or a Mn adequate/control diet (MnA) (<1 and 12 mg/kg Mn, respectively) for a 14-wk period. We investigated endothelium-dependent vasodilation induced by acetylcholine (Ach; 10(-8) to 3 x 10(-6) mol/L) in isolated 3-mm aortic rings precontracted with l-phenylephrine (l-Phe; 10(-6) mol/L). Seven concentrations of Ach were used in the presence or absence of inhibitors of nitric oxide synthase and cyclo-oxygenase. After a second precontraction, 8 doses of sodium nitroprusside (SNP; 10(-8) to 10(-5) mol/L) were added to assess endothelium-independent vasodilation. We observed a decrease in Ach-induced and SNP-induced vasodilation in MnD rat aortas when compared with MnA rat aortas (P </= 0.05). Vessel sensitivity of MnD and MnA aortas to Ach was similar. The addition of l-arginine had no effect on nitric oxide-mediated vasodilation in either group. Nitric oxide synthase-inhibition blunted endothelium-dependent vasodilation to the same degree for both diet groups. Cyclo-oxygenase inhibition enhanced both Ach-induced and SNP-induced vasodilation of MnD rings compared with MnA aortic rings (P </= 0.05). Manganese inhibits the synthesis or activity of a prostanoid-derived vasoconstrictor, which seems to be present at basal and at stimulated levels. This effect is independent of membrane-related events. Our results provide further information on the critical role of Mn on vasomotor tone.
authors.affiliation: Department Physiology and Biophysics, School of Medicine, University of Louisville, KY 40292, USA.
authors.forename: Anastasia Z
authors.initials: AZ
authors.lastname: Kalea
authors.forename: Dale A
authors.initials: DA
authors.lastname: Schuschke
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Harris
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Klimis-Zacas
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004032:Diet; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000172:deficiency*; D009119:Muscle Contraction / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D008345:Manganese; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine