RESUMEN
BACKGROUND: Nitric oxide is an endothelium dependent dilator, which may protect against atherosclerosis. Several studies have shown a decrease in nitric oxide activity with aging, however none have assessed aging and atherosclerosis separately. We tested the hypothesis that aging blunts both basal and receptor-mediated endothelial nitric oxide release in humans. METHODS: We examined whether forearm blood flow responses to intra-arterial acetylcholine, and nitroprusside, were altered with aging, with and without co-infusion of an inhibitor of nitric oxide synthase (N(G)-mono-methyl-L-arginine) in three groups of human subjects; a group with clinical atherosclerotic vascular disease (n = 31, 21 M), otherwise healthy elderly (n = 17, 13 M), and healthy young controls (n = 15, 8 M). RESULTS: There was no difference in basal flows between the three groups. There was also no difference in the dilatation to either acetylcholine or nitroprusside responses between the AVD and the healthy elderly group; however, aging significantly decreased acetylcholine or nitroprusside responses when compared to the young controls (p < 0.02). Furthermore, the ratio between acetylcholine and nitroprusside, a marker of endothelial NO synthase activity, was significantly greater in the young volunteers (0.816 +/- 0.094% vs. 0.892 +/- 0.146 % vs. 1.389 +/- 0.2%, in atherosclerotic vascular disease, healthy elderly group, and young controls respectively). CONCLUSIONS: Forearm blood flow responses to endothelium dependent and independent stimuli are blunted with aging, independent of the presence of atherosclerotic disease. Moreover, the normal aging process may induce significant global vascular dysfunction (involving the endothelium and the vascular smooth muscle); to as great a degree as clinically manifest atherosclerosis.
Asunto(s)
Envejecimiento , Enfermedad de la Arteria Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Músculo Liso Vascular/fisiopatología , Óxido Nítrico/metabolismo , Acetilcolina/administración & dosificación , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/metabolismo , Estudios Cruzados , Endotelio Vascular/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Femenino , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Nitroprusiato/administración & dosificación , Flujo Sanguíneo Regional/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación , omega-N-Metilarginina/administración & dosificaciónAsunto(s)
Diabetes Mellitus Tipo 2/etnología , Síndrome Metabólico/etnología , Población Blanca/estadística & datos numéricos , Adulto , Índice de Masa Corporal , Comparación Transcultural , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , India/etnología , Resistencia a la Insulina , Masculino , Síndrome Metabólico/diagnóstico , Riesgo , Estados Unidos , Relación Cintura-CaderaRESUMEN
Homocysteine may contribute to systolic hypertension and cardiac events by decreasing conduit artery compliance and inducing endothelial dysfunction. The effects of the experimental induction of hyperhomocysteinemia on systemic arterial compliance and pulsewave velocity are unclear, with contradictory results from previous studies. The investigators tested whether oral methionine impairs brachial artery compliance in addition to endothelial function.
Asunto(s)
Hiperhomocisteinemia/inducido químicamente , Metionina/farmacología , Administración Oral , Adulto , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Modelos Lineales , Masculino , Metionina/administración & dosificación , Ultrasonografía DopplerRESUMEN
Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal. Studies using surrogate markers of atherosclerosis have suggested a possible role of ezetimibe in combating atherosclerosis. Ezetimibe provides an effective therapeutic strategy for the management of homozygous familial hypercholesterolemia (HoFH) and sitosterolemia. The lack of outcomes and long term safety data is attributed to the relatively recent introduction of this medication.
RESUMEN
Nicotinic acid is a unique cholesterol modifying agent that exerts favorable effects on all cholesterol parameters. It holds promise as one of the main pharmacological agents to treat mixed dyslipidemia in metabolic syndrome and diabetic patients. The use of nicotinic acid has always been haunted with concerns that it might worsen insulin resistance and complicate diabetes management. We will discuss the interaction between phosphorous metabolism and carbohydrate metabolism and the possibility that worsening of insulin resistance could be related to a drug induced alteration in phosphorous metabolism, and the implications of that in medical management of diabetes and metabolic syndrome patients with mixed dyslipidemia.