title: Role of nitric oxide and prostaglandin systems in lithium modulation of acetylcholine vasodilation.
abstract: The mechanism of lithium action, an effective treatment for bipolar disease, is still unknown. The present study examined the role of nitric oxide (NO) and prostaglandin systems in lithium modulation of acetylcholine in mesenteric vascular bed of rats by cannulating superior mesenteric artery. Acetylcholine (ACh) or sodium nitroprusside was injected under constant controlled flow induced by phenylephrine; therefore, changes in perfusion pressure reflect changes in resistance. Although 0.5 mM or 1 mM lithium-pretreatment of vascular bed causes reduction in ACh-response, 1.5 mM lithium induced no changes and 2 and 2.5 mM lithium potentiated ACh-induced mesenteric vascular bed relaxation compared to control group. Pretreatment of vascular bed with L-NAME or indomethacin decreased ACh-induced relaxation in 2 concentrations of 0.5 and 2 mM of lithium. The vasorelaxation response to sodium nitroprusside, the NO donor, was not different among lithium groups (0.5 and 2 mM) and controls. In conclusion, there is a dual modulation of endothelium-dependent relaxation, including an inhibitory effect at lower dose and a stimulating effect at higher dose of lithium in rat mesenteric vascular bed. NO synthesis or cyclooxygenase inhibition decreased vasorelaxation in both lower and higher doses of lithium, suggesting a role for NO and prostaglandin in this effect.
authors: Department of Pharmacology, School of Medicine, Medical Sciences/Tehran University, Tehran, Iran.
authors: Bahareh
authors: B
authors: Rahimzadeh-Rofouyi
authors: Banafsheh
authors: B
authors: Afsharimani
authors: Leila
authors: L
authors: Moezi
authors: Farzad
authors: F
authors: Ebrahimi
authors: Shahram Ejtemaei
authors: SE
authors: Mehr
authors: Tajmah
authors: T
authors: Mombeini
authors: Mohammad Hosein
authors: MH
authors: Ghahremani
authors: Ahmad R
authors: AR
authors: Dehpour
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D018021:Lithium Chloride; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin