title: Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.
abstract: Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.
authors.affiliation: Toyama Institute for Cardiovascular Pharmacology Research, 7-13, 1-Chome, Azuchimachi, Chuo-ku, Osaka, 541-0052, Japan. n.toda.toyama-bldg@orion.ocn.ne.jp.
authors.forename: Noboru
authors.identifier: 0000-0003-4035-7365
authors.initials: N
authors.lastname: Toda
authors.affiliation: Department of Pharmacology, Shiga University of Medical Science, Seta, Otsu, Shiga, 520-2192, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation; D003326:Coronary Circulation; D006801:Humans; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*
chemical_list: D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III
keywords: Cerebral blood flow; Coronary blood flow; Hyperhomocysteinemia; Nitric oxide; Oxidative stress