Investigation of the inhibitory effects of homocysteine and copper on nitric oxide‐mediated relaxation of rat isolated aorta

• Published in: British journal of pharmacology Vol. 126; no. 4; pp. 1034 - 1040
• Main Authors: Emsley, Alison M, Jeremy, Jamie Y, Gomes, Guiomar N, Angelini, Gianni D, Plane, Frances
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.1999; Nature Publishing
• Subjects: Acetylcholine - pharmacology; Animals; Aorta - drug effects; Aorta - physiology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Catalase - pharmacology; copper; Copper - pharmacology; Dose-Response Relationship, Drug; Endothelium, Vascular - physiology; Homocysteine; Homocysteine - pharmacology; In Vitro Techniques; Male; Medical sciences; nitric oxide; Nitric Oxide - physiology; Rats; Rats, Inbred WKY; Superoxide Dismutase - pharmacology; Vasodilation - drug effects; Rat; Pathogenesis; Cardiovascular disease; Smooth muscle; Superoxide dismutase; Vasodilation; Blood plasma; Vascular disease; Blood vessel; Atherosclerosis; Aorta; Copper; Enzyme; Rodentia; Inflammation; Antioxidant; Hydrogen Peroxides; In vitro; Endothelium; Sulfur containing aminoacid; Muscular relaxation; Vertebrata; Hyperoxides; Mammalia; Animal; Nitric oxide; Oxidoreductases; Circulatory system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702374

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. Exposure to HC (10–100 μM; 30 min) had no effect on relaxation to acetylcholine (ACh; 0.01–10 μM, 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 μM, 180 min, n=6). Exposure to HC (100 μM) and copper (10–100 μM; 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). HC and copper (100 μM; 30 min) significantly inhibited endothelium‐independent relaxation to glyceryl trinitrate (0.01–10 μM; n=8). In contrast, HC (1 mM), alone or in combination with copper (100 μM), did not inhibit relaxation to the endothelium‐independent relaxant sodium nitroprusside (0.01–10 μM; n=4). 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. British Journal of Pharmacology (1999) 126, 1034–1040; doi:10.1038/sj.bjp.0702374