OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.

OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated) showed an increase on mean blood pressure compared with normotensive ones (controls and denervated). Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

OBJETIVO: avaliar o estresse oxidativo em tecido cardíaco de ratas ooforectomizadas, com ou sem terapia hormonal. MÉTODOS: ratas Wistar foram divididas em três grupos: grupo controle (GC), grupo ooforectomizada (GO) e grupo ooforectomizada + suplementação hormonal (GOS). A privação estrogênica foi obtida pela ooforectomia bilateral. Uma semana após a ooforectomia, um pellet de 1,5 mg de 17beta-estradiol foi implantado nos animais do grupo GOS. Nove semanas após a ooforectomia, o tecido cardíaco foi obtido para a análise do estresse oxidativo por meio da medida da quimiluminescência e da atividade das enzimas antioxidantes catalase (CAT), superóxido dismutase (SOD) e glutationa peroxidase (GPx). RESULTADOS: a quimiluminescência estava aumentada no GO (7348±312 cps/mg proteína) quando comparado ao GC (6250±41 cps/mg proteína, p<0,01), mas não houve diferença significante entre GC e GOS (6170±237 cps/mg proteína). A ooforectomia reduziu a atividade da SOD (22%, p<0,001) e da CAT (35%, p<0,05) no GO comparado ao GC. A terapia hormonal normalizou a atividade das enzimas antioxidantes no GOS. Não houve significância estatística na atividade da GPx quando os grupos estudados foram comparados. CONCLUSÕES: a privação dos hormônios ovarianos induziu aumento do estresse oxidativo e redução das defesas antioxidantes no tecido cardíaco. No entanto, a terapia hormonal preveniu o estresse oxidativo após a ooforectomia, provavelmente devido a um aumento das enzimas CAT e SOD no músculo cardíaco. Esses achados sugerem uma importante participação do estresse oxidativo nas disfunções cardiovasculares observadas em mulheres após a menopausa, reforçando a importância da terapia hormonal para o manejo dos riscos de doenças cardiovasculares neste grupo de mulheres.

PURPOSE: to evaluate oxidative stress in cardiac tissue of ovariectomized rats, with and without hormonal therapy. METHODS: female Wistar rats were divided in three groups: control group (CG); ovariectomized group (OG); ovariectomized group with estrogen supplementation (ESG). The estrogen deprivation was done through bilateral ovariectomy. After one week from the ovariectomy, a pellet of 1.5 mg of 17beta-estradiol was implanted in the ESG animals. Nine weeks after the ovariectomy, cardiac tissue was obtained for the analysis of the oxidative stress through CL (chemiluminescence), and measurement of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and gluthatione peroxidase (GPx). RESULTS: CL was increased in the OG (7348±312 cps/mg protein) when compared with the CG (6250±41 cps/mg protein, p<0.01), but there was no significant difference between the CG and the ESG (6170±237 cps/mg protein). Ovariectomy reduced SOD (35%, p<0.05) and CAT (22%, p<0.001) activities in the OG as compared with the CG. Hormonal therapy normalized antioxidant enzymes activities in the ESG. There was no statistically significant difference in GPx activity among the groups studied. CONCLUSIONS: ovarian hormone deprivation induced an increase of oxidative stress with reduction of antioxidant defenses in the cardiac tissue. However, hormonal therapy prevented oxidative stress after ovariectomy, probably due to an increase of the CAT and SOD activities in the cardiac muscle. These findings suggest an important oxidative stress contribution in cardiovascular dysfunctions observed in women after menopause, reinforcing the importance of hormonal therapy in the management of cardiovascular diseases risk in this group of women.