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 L-histamina e de antagonistas histaminérgicos sobre a recuperação funcional após hemilabirintectomia em Carassius auratus.

The aim of this study was to verify the effects of histamine on the process of functional recovery after hemilabyrinthectomy in goldfish, Carassius auratus. To this end, the fish were submitted to unilateral vestibular lesion and treated with a histamine precursor (L-histidine) and antagonists of the receptors H1, H2 and H3 (respectively chlorpheniramine, zolantidine and thioperamide). The success of the surgery was evidenced by the ataxia they suffered during approximately thirty minutes of observation and the presence of these signs was used as criterion for the inclusion of the animal in the experiment. The subjects were treated during fifteen consecutive days with L-histidine (150 mg/kg), chlorpheniramine (24 mg/kg), zolantidine (18 mg/kg) and thioperamide (15 mg/kg). All substances were administrated in a volume of 1.5 ml/ kg of body weight and sterile saline (1.5 ml/kg) was used with the experimental control group. Another group, the sham lesion group, was submitted to the same surgical procedure, but in this case the vestibular lesion was not carried out. The subjects were submitted to seven tests, the first test being carried out on the first day after the lesion, and then five more at three day intervals. The seventh test was carried out three days after the conclusion of treatment. In each test, the subject was placed inside a translucent tube inside a black aquarium which was illuminated on the ipsilateral side for five minutes. The fish behavior was recorded with a video camera located in front of a small opening in the front wall of the aquarium. Body tilt was measured by comparing a line traced between the subject s eyes with a horizontal line traced on the television screen. The mean of the tilt in degrees obtained every thirty seconds was considered. The data were subjected to variance analysis (Two-way ANOVA), followed by the Student Newman Keuls multiple comparisons test.O objetivo deste estudo foi verificar os efeitos da histamina sobre o processo de recuperação funcional, após hemilabirintectomia em peixes da espécie Carassius auratus. Para tanto, foram utilizados a L-histidina, um precursor histaminérgico e antagonistas dos receptores H1, H2 e H3, sendo a clorfeniramina, antagonista H1, a zolantidina antagonista H2 e a tioperamida, antagonista do receptor histaminérgico H3. Os peixes foram anestesiados e submetidos à lesão vestibular unilateral. O sucesso da cirurgia foi evidenciado pela ataxia, caracterizada pelo rolamento do corpo e nado incoordenado durante aproximadamente trinta minutos, e a presença desses sinais foi utilizada como critério de inclusão do animal no experimento. Os sujeitos foram tratados durante quinze dias consecutivos com L-histidina (150 mg/kg), clorfeniramina (24 mg/kg), zolantidina (18 mg/kg) e tioperamida (15 mg/kg). Todas as substâncias foram administradas em um volume de 1.5 ml/kg, e a salina estéril (1.5 ml/kg) foi utilizada como controle experimental. Um outro grupo foi submetido ao procedimento cirúrgico, mas a lesão vestibular não foi realizada (Lesão Fictícia). Os sujeitos foram submetidos a sete testes. O primeiro teste foi realizado no primeiro dia após a lesão, e os demais, a cada três dias, totalizando seis testes. O sétimo teste foi realizado três dias após o término do tratamento. Cada teste consistiu em posicionar o sujeito dentro de um cilindro, no interior de um aquário revestido com uma película preta e iluminar esse aquário no lado ipsilateral à lesão durante cinco minutos. O comportamento animal foi registrado através de uma câmera de vídeo posicionada em frente a uma pequena abertura presente na parede anterior do aquário. O ângulo de inclinação corporal foi formado por uma linha correspondente ao posicionamento dos olhos e uma linha horizontal e medido com um transferidor na tela do televisor. A média desses ângulos obtidos a cada trinta segundos foi considerada. Os dados foram analisados através da Análise de Variância (ANOVA) de duas vias, seguida do teste de comparações múltiplas de Student Newman Keuls

Baroreflex Sensitivity Impairment Is Associated With Cardiac Diastolic Dysfunction in Rats

Background: Studies have shown that the autonomic dysfunction accompanied by impaired baroreflex sensitivity was associated with higher mortality. However, the influence of decreased baroreflex sensitivity on cardiac function, especially in diastolic function, is not well understood. This study evaluated the morpho-functional changes associated with baroreflex impairment induced by chronic sinoaortic denervation (SAD). Methods and Results: Animals were divided into sinoaortic denervation (SAD) and control (C) groups. Baroreflex sensitivity was evaluated by tachycardic and bradycardic responses, induced by vasoactive drugs. Cardiac function was studied by echocardiography and by left ventricle (LV) catheterization. LV collagen content and the expression of regulatory proteins involved in intracellular Ca(2+) homeostasis were quantified. Results showed higher LV mass in SAD versus C animals. Furthermore, an increase in deceleration time of E-wave in the SAD versus the C group (2.14 +/- 0.07 ms vs 1.78 +/- 0.03 ms) was observed. LV end-diastolic pressure was increased and the minimum dP/dt was decreased in the SAD versus the C group (12 +/- 1.5 mm Hg vs 5.3 +/- 0.2 mm Hg and 7,422 +/- 201 vs 4,999 +/- 345 mm Hg/s, respectively). SERCA/NCX ratio was lower in SAD than in control rats. The same was verified in SERCA/PLB ratio. Conclusions: The results suggest that baroreflex dysfunction is associated with cardiac diastolic dysfunction independently of the presence of other risk factors. (J Cardiac Fail 2011;17:519-525)Fundacao Zerbini, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP