title: Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta.
abstract: 1. Elevated plasma levels of homocysteine (HC) and copper have both been associated with the development of inflammatory vascular diseases, such as atherosclerosis. In this study, the effects of a combination of HC and copper on nitric oxide (NO)-mediated relaxation of isolated rat aortic rings were investigated. 2. Exposure to HC (10-100 microM; 30 min) had no effect on relaxation to acetylcholine (ACh; 0.01-10 microM, n=4). Pre-incubation of aortic rings with a higher concentration of HC for an extended period (1 mM; 180 min) significantly inhibited endothelium-dependent relaxation (n=4), but this inhibition was prevented by the presence of the copper chelator bathocuprione (10 microM, 180 min, n=6). 3. Exposure to HC (100 microM) and copper (10-100 microM; 30 min) caused a copper concentration-dependent inhibition of endothelium-dependent relaxation (n=4). This inhibitory effect was reduced in the presence of either superoxide dismutase (SOD; 100 u ml(-1); n=4) or catalase (100 u ml(-1); n=4), and further reduced by the presence of both enzymes (n=5). 4. HC and copper (100 microM; 30 min) significantly inhibited endothelium-independent relaxation to glyceryl trinitrate (0.01-10 microM; n=8). In contrast, HC (1 mM), alone or in combination with copper (100 microM), did not inhibit relaxation to the endothelium-independent relaxant sodium nitroprusside (0.01-10 microM; n=4). 5. These data indicate that the presence of copper greatly enhances the inhibitory actions of HC on NO-mediated relaxation of isolated aortic rings. The reduction of inhibition by catalase and SOD indicates a possible role for copper-catalyzed generation of superoxide and hydrogen peroxide leading to an increased inactivation or decreased production of endothelium-derived NO.
authors: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, England, UK.
authors: A M
authors: AM
authors: Emsley
authors: J Y
authors: JY
authors: Jeremy
authors: G N
authors: GN
authors: Gomes
authors: G D
authors: GD
authors: Angelini
authors: F
authors: F
authors: Plane
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006710:Homocysteine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D006710:Homocysteine; D009569:Nitric Oxide; D003300:Copper; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine