Baroreflex deficit are associated with target organ damage / Os déficits de barorreflexo estão associados ao dano do órgão alvo

As is well known, there are different pathophysiological conditions in which baroreflex deficit is enrolled in end-organ damage like hypertension, heart failure and myocardial infarction. The purpose of this study was to investigate the mechanisms enrolled in those relationships using a baroreflex deficit­induced model. Sinoaortic-denervated (SAD) rats were used as a model of arterial baroreflex impairment. Male Wistar rats were divided into: control (n = 9), and SAD (n = 8, 30 days) groups. SAD was performed using the method previously described by Krieger (1964). Cardiac morphology was assessed by echocardiography BP, HR and BP, and pulse interval (PI) variabilities were analyzed using a data acquisition system (Codas, 2kHz). Stroke volume and peripheral and regional resistance were evaluated using colored microspheres. SAD induced LV hypertrophy estimated by LV/BW mass using echocardiography. BP (C: 106±0.6 vs. SAD: 108±2 mmHg) and HR (C: 355±7 vs. SAD: 357±15 bpm) were not modified by SAD, while BP variability (C: 6.2±0.84 vs SAD: 14±0.9 mmHg) and PI variability (C: 24±0.7 vs SAD:17±0.8 ms) were increased and decreased, respectively. Moreover, a reduction was observed in stroke volume (C: 0.31±0.02 vs SAD: 0.25±0.01 mL/ min) and an increase in total peripheral resistance (C: 0.97±0.07 vs. SAD: 1.23±0.07 mL/min/mmHg) in SAD animals. Those alterations resulted in increased cardiac vascular resistance (C: 35±1.6 vs. SAD:66±2.3 mmHg/mL/min/g) and renal vascular resistance (C: 31±1.2 vs. SAD: 75±2.2 mmHg/mL/min/g) in the SAD group. SAD induced an augment in cardiac and renal damage as cardiac morphology by histological techniques showed increased arterial wall and interstitial fibroses, and renal morphology showed interstitial fibroses and a decreased Bowmann space. Conclusion: Total baroreflex dysfunction impaired BP and HR variabilities associated with decreased stroke volume and increased peripheral and regional resistance. These adjustments may play an important role in target organ damage in different pathological conditions; even BP values were maintained at the control levels

Existem diferentes condições fisiopatológicas em que o déficit de barorreflexo está associado ao dano do órgão final, como hipertensão, insuficiência cardíaca e infarto do miocárdio. O objetivo deste estudo foi investigar os mecanismos inscritos nestes relacionamentos usando um modelo induzido por déficit de barorreflexo. Foram utilizados ratos com desnervação sino-aórtica (SAD) como modelo de comprometimento barorreflexo arterial. Os ratos Wistar machos foram divididos em grupos controle (n = 9) e SAD (n = 8, 30 dias). O SAD foi realizado utilizando o método anteriormente descrito por Krieger (1964). A morfologia cardíaca foi avaliada pela ecocardiografia PA, e as variabilidades de FC e PA, e do intervalo de pulso (IP) foram analisadas usando um sistema de aquisição de dados (Codas, 2kHz). O volume sistólico e a resistência periférica e regional foram avaliados utilizando microesferas coloridas. SAD induziu hipertrofia do VE estimada pela massa de VE/PC usando ecocardiografia. PA (C: 106±0,6 vs. SAD: 108±2 mmHg) e FC (C: 355±7 vs. SAD: 357±15 bpm) não foram modificados pelo SAD, enquanto a variabilidade da PA (C: 6,2±0,84 vs. SAD: 14±0,9 mmHg) e a variabilidade de PI (C: 24±0,7 vs. SAD: 17±0,8 ms) aumentaram e diminuíram, respectivamente. Além disso, observou-se uma redução no volume sistólico (C: 0,31± 0,02 vs SAD: 0,25 ± 0,01 mL/min) e um aumento na resistência periférica total (C: 0,97±0,07 vs. SAD: 1,23±0,07 mL/min/mmHg) em animais SAD. Essas alterações resultaram em aumento da resistência vascular cardíaca (C: 35±1,6 vs. SAD: 66 ± 2,3 mmHg/mL/min/g) e resistência vascular renal (C: 31±1,2 vs. SAD: 75±2,2 mmHg/mL/min/g) no grupo SAD. SAD induziu um aumento no dano cardíaco e renal como a morfologia cardíaca por técnicas histológicas mostrou aumento da parede arterial e fibrose intersticial, e a morfologia renal mostrou fibrose intersticial e uma diminuição do espaço de Bowmann. A disfunção barorreflexa total prejudicou as variabilidades de PA e FC associadas à diminuição do volume sistólico e ao aumento da resistência periférica e regional. Esses ajustes podem desempenhar um papel importante no dano de órgãos alvo em diferentes condições patológicas; até mesmo os valores da PA foram mantidos nos níveis de controle

Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

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.

Efeitos da suplementação do 17beta-estradiol no dano oxidativo cardíaco de ratas submetidas à privação dos hormônios ovarianos / Effects of 17beta-estradiol replacement on cardiac oxidative damage in rats submitted to ovarian hormone deprivation

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 por cento, p<0,001) e da CAT (35 por cento, 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 percent, p<0.05) and CAT (22 percent, 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.