title: Adult rats are more sensitive to the vascular effects induced by hyperhomocysteinemia than young rats.
abstract: We aimed to investigate the vascular effects of hyperhomocysteinemia (HHcy) on carotid arteries from young and adult rats. With this purpose young and adult rats received a solution of DL-homocysteine-thiolactone (1 g/kg body weight/day) in the drinking water for 7, 14 and 28 days. Increase on plasma homocysteine occurred in young and adult rats treated with DL-homocysteine-thiolactone in all periods. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy enhanced the contractile response of endothelium-intact, carotid rings to phenylephrine in both young and adult rats. However, in young rats, the increased phenylephrine-induced contraction was observed after hyperhomocysteinemia for 14 and 28 days, whereas in adult rats this response was already apparent after 7 day treatment. HHcy impaired acetylcholine-induced relaxation in arteries from adult but not young rats. The contraction induced by phenylephrine in carotid arteries in the presence of Y-27632 was reversed to control values in arteries from young but not adult rats with hyperhomocysteinemia. HHcy did not alter the contraction induced by CaCl(2) in carotid arteries from young rats, but enhanced CaCl(2)-induced contraction in the arteries from adult rats. HHcy increased the basal levels of superoxide anion in arteries from both groups. Finally, HHcy decreased the basal levels of nitrite in arteries from adult but not young rats. The major new finding of the present work is that arteries from young rats are more resistant to vascular changes evoked by HHcy than arteries from adult rats. Also, we verified that the enhanced vascular response to phenylephrine observed in carotid arteries of DL-homocysteine thiolactone-treated rats is mediated by different mechanisms in young and adult rats.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Claudia Roberta
authors.initials: CR
authors.lastname: de Andrade
authors.forename: Glenda Andréa Déstro
authors.initials: GA
authors.lastname: de Campos
authors.forename: Carlos Renato
authors.initials: CR
authors.lastname: Tirapelli
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: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D000577:Amides; D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D014662:Vasoconstrictor Agents; D006710:Homocysteine; D013481:Superoxides; C108830:Y 27632; D010656:Phenylephrine; D009569:Nitric Oxide; C007957:homocysteine thiolactone; D054460:rho-Associated Kinases; D002122:Calcium Chloride; D000109:Acetylcholine; D007213:Indomethacin