RESUMEN
OBJECTIVE: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial, and the presence of insulin resistance is recognized as the pathophysiological hallmark of this condition. Arterial hypertension is referred as an insulin-resistant state, and insulin resistance may substantially contribute to the cardiovascular risk in this disorder. We examined the inter-relationship between insulin sensitivity, adiponectin levels, and NAFLD in hypertensive patients with different circadian blood pressure profiles. METHODS: Eighty never-treated patients with essential hypertension were selected for having a nocturnal decrement of blood pressure that was at least 10% (dippers, n=47) or less than 10% (nondippers, n=33) of daytime values. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for hepatic disease. The two groups were similar as to sex, age, and BMI. Abdominal fat distribution and NAFLD were assessed by ultrasonography. RESULTS: Hepatic steatosis was detected in 57.5% of all patients. Nondippers showed a higher prevalence of NAFLD than dippers (81.8 vs. 40.4%, P<0.005). Insulin and the homeostasis model of assessment index were higher (P<0.001) and adiponectin was lower (P<0.001) in nondippers than in dippers, whereas no difference was found in regional fat, liver enzymes, and other metabolic parameters. At multivariate analysis, factors independently associated with nondipping were insulin (P<0.05) and adiponectin (P<0.01) with the homeostasis model of assessment index being of borderline significance. CONCLUSION: In the absence of major risk factors for the development of NAFLD, a high prevalence of liver steatosis was associated with insulin resistance and low adiponectin levels in essential hypertensive patients with a nondipping profile.
Asunto(s)
Ritmo Circadiano , Hígado Graso/patología , Hipertensión/patología , Resistencia a la Insulina/fisiología , Adiponectina/sangre , Adolescente , Adulto , Anciano , Presión Sanguínea , Hígado Graso/sangre , Hígado Graso/complicaciones , Femenino , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Insulina/sangre , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , UltrasonografíaRESUMEN
OBJECTIVE: To gain insight into the regulation of cardiac apoptosis we studied the dose-response and time-course effects of angiotensin II (Ang II) infusion on ventricular cardiomyocyte apoptosis and on the expression of Bax and Bcl-2 genes and proteins. STUDY DESIGN AND METHODS: In the dose-response study, Ang II was infused subcutaneously at doses of 100, 200, 400, 800 and 1200 ng/kg per min for 14 days. In the time-course study, rats infused with Ang II at doses of 200 and 400 ng/kg per min were followed for 7 and 14 days. The cardiomyocyte apoptotic density was assessed by DNA end labelling (terminal deoxynucleotide nick-end labelling; TUNEL). Gene and protein expression of Bcl-2 and Bax were evaluated by reverse transcriptase-polymerase chain reaction and by Western blots. RESULTS: Systolic blood pressure and left ventricular mass were increased in a dose-dependent manner in Ang II-infused rats. A statistically significant increase in the rate of cardiac apoptosis and pro-apoptotic changes of Bcl-2 and Bax gene and protein expression was observed when high doses of Ang II (800-1200 ng/kg per min) were infused. A positive correlation of apoptotic density with Bax and a negative correlation with Bcl-2 and Bcl-2/Bax ratio were found. Cardiac apoptosis was greatly influenced by the timing of Ang II infusion. Losartan-treated Ang II-infused rats exhibited normalized systolic blood pressure, left ventricular weight, apoptosis, and Bax and Bcl-2 levels. CONCLUSIONS: Our results are consistent with the pathophysiological role of Ang II in induction of cardiac apoptosis, and explain the cardioprotective effect of Ang II receptor antagonists.