RESUMO
BACKGROUND: Nitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO. AIM: To determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE-/- mouse fed a high fat diet (HFD). METHODS AND RESULTS: ApoE-/- fed a HFD were randomized to receive (i) high nitrate (10mmol/kg/day, n=12), (ii) moderate nitrate (1mmol/kg/day, n=8), (iii) low nitrate (0.1mmol/kg/day, n=8), or (iv) sodium chloride supplemented drinking water (control, n=10) for 10 weeks. A group of C57BL6 mice (n=6) received regular water and served as a healthy reference group. At 10 weeks, ACh-induced vessel relaxation was significantly impaired in ApoE-/- mice versus C57BL6. Mice supplemented with low or moderate nitrate showed significant improvements in ACh-induced vessel relaxation compared to ApoE-/- mice given the high nitrate or sodium chloride. Plaque collagen expression was increased and lipid deposition reduced following supplementation with low or moderate nitrate compared to sodium chloride, reflecting increased plaque stability with nitrate supplementation. Plasma nitrate and nitrite levels were significantly increased in all three groups fed the nitrate-supplemented water. CONCLUSION: Low and moderate dose nitrate significantly improved endothelial function and atherosclerotic plaque composition in ApoE-/- mice fed a HFD.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/dietoterapia , Suplementos Nutricionais , Nitratos/administração & dosagem , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico/metabolismo , Placa Aterosclerótica/dietoterapia , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/deficiência , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/patologia , Colágeno/genética , Colágeno/metabolismo , Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nitratos/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Técnicas de Cultura de Tecidos , Vasodilatação/efeitos dos fármacosRESUMO
Prostate cancer early detection choices and treatment options are fraught with controversy. To update the consultation-liaison psychiatrist who works with at-risk men, the authors reviewed all pertinent citations in the medicine database from 1966 to 1998 and in other relevant publications. Though watchful waiting for early-stage prostate cancer has no side effects, men must cope psychologically with issues of long-term cancer survivorship. Men can choose between different treatment options (e.g., radiation vs. radical prostatectomy) with early detection. Urinary incontinence, sexual dysfunction, and fatigue are major emotional and physical stressors for this population. Consultation-liaison psychiatrists and physicians need to be aware of the psychosocial sequelae of both prostate cancer and treatment-related side effects.
