title: Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries.
abstract: Homocysteine is an independent risk factor for coronary heart disease, as well as for cerebrovascular and peripheral vascular diseases. The purpose of this study was to investigate the effects of hyperhomocysteinemia (HHcy) on vascular reactivity within carotid artery segments isolated from ovariectomized female rats. Treatment with DL-Hcy thiolactone (1 g/kg body weight per day) reduced the phenylephrine-induced contraction of denuded rings. However, the treatment did not alter KCl-induced contractions, or relaxations induced by sodium nitroprusside or acetylcholine. We report elevated expressions of iNOS, eNOS, and nitrotyrosine in homocysteine-treated rat artery sections. Moreover, the inhibition of NOS by L-NAME, 1,400 W, or L-NNA restored phenylephrine-induced vasoconstriction in carotid artery segments from Hcy-treated rats. In conclusion, our findings show that severe HHCy can promote an acute decrease in the endothelium-independent contractile responses of carotid arteries to adrenergic agonists. This effect was restored by nitric oxide synthase inhibitors, which further supports the involvement of nitric oxide in HHcy-derived vascular dysfunction.
authors.affiliation: Laboratory of Pharmacology, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Avenida do Café 3900, Ribeirão Preto, SP, CEP 14040-903, Brazil. acarla_c@yahoo.com
authors.forename: Andréa Carla
authors.initials: AC
authors.lastname: Celotto
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Fukada
authors.forename: Francisco R M
authors.initials: FR
authors.lastname: Laurindo
authors.forename: Renato
authors.initials: R
authors.lastname: Haddad
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000201:enzymology / Q000503:physiopathology*; D002908:Chronic Disease; D005260:Female; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000503:physiopathology*; D007150:Immunohistochemistry; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019001:Nitric Oxide Synthase