RESUMEN
The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin-angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin-angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control.
Asunto(s)
Isquemia Encefálica/genética , Predisposición Genética a la Enfermedad , Hemostasis/genética , Polimorfismo de Nucleótido Simple , Sistema Renina-Angiotensina/genética , Accidente Cerebrovascular/genética , Anciano , Alelos , Isquemia Encefálica/epidemiología , Femenino , Frecuencia de los Genes/genética , Humanos , Masculino , Persona de Mediana Edad , Federación de Rusia/epidemiología , Accidente Cerebrovascular/epidemiologíaRESUMEN
Similar degree of glycemia (28-31 mmol/liter) and similar mortality (37-42%) were revealed in August rats exhibiting enhanced activity of NO system and in Wistar rats 3 weeks after alloxan treatment. Under conditions of myocardial ischemia caused by 10-min coronary artery ligation, the intensity of arrhythmias did not differ from the control in Wistar rats with diabetes mellitus and increased in August rats. Under conditions of reperfusion, diabetes produced an antiarrhythmic effect in Wistar rats and did not affect arrhythmia in August rats. Plasma concentrations of nitrates and nitrites in Wistar and August rats increased by 82 and 143%, respectively, compared to the control. The level of hemoxygenase-1 (hsp32) in the myocardium remained unchanged in Wistar rats and decreased by 26% in August rats. Thus, the absence of antiarrhythmic effect of acute diabetes in August rats is probably related to elevated NO content and reduced antioxidant activity.
Asunto(s)
Arritmias Cardíacas/etiología , Arritmias Cardíacas/metabolismo , Diabetes Mellitus Experimental/complicaciones , Óxido Nítrico/metabolismo , Daño por Reperfusión/complicaciones , Animales , Western Blotting , Hemo Oxigenasa (Desciclizante)/metabolismo , Miocardio/metabolismo , Nitratos/sangre , Nitritos/sangre , Ratas , Ratas Endogámicas , Ratas Wistar , Estadísticas no ParamétricasRESUMEN
UNLABELLED: Heart function was studied in the August rats with innate raised sympathetic-adrenal system and in the Wistar rats through the period of 3 month after myocardial infarction. The sizes of the postinfarction scars were similar in the rats under comparison (56-62%) but end-diastolic pressure in Wistar rats and in August rats was 18.7 +/- 2.2 mm Hg and 11.8 +/- 0.7 mm Hg. Under the maximum isometric load induced by the aorta coarctation, the work efficiency of the heart in the August rats was greater than in the Wistar rats. During the postinfarction period, plasma catecholamine (CA) in August rats was higher than in Wistar rats. In the adrenal glands, the CA contents in August rats increased and in Wistar rats decreased. The activity of CA resynthes in the adrenal glands and in the hypothalamus in August rats did not change and in Wistar rats increased. The blood contents of nitrate and nitrite and hemine oxygenase-1 level in the myocardium of August rats were increased in contrast to Wistar rats. THE CONCLUSION: the higher viability of the myocardium in August rats with long existing postinfarction cardiasclerosis is to a considerable extent associated with lowered activation of the sympathetic-adrenal system under more expressing activation of NO-system and antioxidant protection.
Asunto(s)
Glándulas Suprarrenales/fisiopatología , Corazón/fisiopatología , Hipotálamo/fisiopatología , Infarto del Miocardio/fisiopatología , Glándulas Suprarrenales/metabolismo , Animales , Aorta/metabolismo , Aorta/fisiopatología , Presión Sanguínea , Catecolaminas/sangre , Cicatriz/sangre , Cicatriz/fisiopatología , Pruebas de Función Cardíaca , Hipotálamo/metabolismo , Infarto del Miocardio/sangre , Miocardio/metabolismo , Ratas , Ratas Endogámicas , Ratas Wistar , Especificidad de la Especie , Factores de TiempoRESUMEN
Three months after myocardial infarction the severity of heart failure and size of postinfarction scars in August rats with inherently reduced adrenoreactivity of the myocardium were similar to those in Wistar rats. The mortality rate in August rats was 2.5-fold lower than in Wistar rats. During the postinfarction period, myocardial adrenoreactivity in August rats remained lower, while the efficiency of cardiac function was 62% higher than in Wistar rats. The incidence of epinephrine-induced arrhythmias in August rats was much lower than in Wistar rats.
Asunto(s)
Infarto del Miocardio/fisiopatología , Receptores Adrenérgicos beta/fisiología , Animales , Catecolaminas/metabolismo , Epinefrina , Infarto del Miocardio/complicaciones , Ratas , Ratas Endogámicas , Ratas Wistar , Esclerosis/etiología , Especificidad de la EspecieRESUMEN
Analysis of contribution of sympathetic and parasympathetic systems into heart rate variability carried out using atenolol and atropine showed that August rats are characterized by enhanced tone of the sympathetic system and reduced tone of the parasympathetic system compared to Wistar rats. Reduced tone of the parasympathetic system is also confirmed by lower sensitivity of the baroreflex. Blockade of NO synthesis with Nw-nitro-L-arginine more markedly increased blood pressure variability in August rats compared to Wistar rats. The data attest to a certain rigidity of the autonomic cardiovascular regulation in August rats.
Asunto(s)
Sistema Nervioso Autónomo/fisiología , Presión Sanguínea , Frecuencia Cardíaca , Antagonistas Adrenérgicos beta/farmacología , Animales , Atenolol/farmacología , Atropina/farmacología , Sistema Nervioso Autónomo/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Ratas , Ratas Wistar , Especificidad de la Especie , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiologíaRESUMEN
Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.