Lateral septal area alpha(1)-and alpha(2)-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats

We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 +/- 0.48 vs food-restricted group = 4.84 +/- 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 +/- 0.44 vs food-restricted group = 7.96 +/- 0.45, and control = 1.52 +/- 0.06 vs food-restricted group = 1.53 +/- 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.

Toxicity of dietary restriction of fat enriched diets on cardiac tissue

The present study examines the effects of caloric restriction in cardiac tissue evaluation markers of oxidative stress. High-fat dietary restrictions can have a long-term impact on cardiac health. Dietary restriction of control diet increased myocardial superoxide dismutase (SOD) and catalase activities. Dietary restriction of fatty acid-enriched diets increased myocardial lipoperoxide concentrations, while SOD activity was decreased in cardiac tissue of rats with dietary restriction of fatty acid-enriched diets. Dietary restriction of unsaturated fatty acid-enriched diet induced the highest lipoperoxide concentration and the lowest myocardial SOD activity. Dietary restriction of unsaturated fatty acid decreased myocardial glycogen, and increased the lactate dehydrogenase/citrate synthase ratio. Dietary restriction of fatty acid-enriched diets were more deleterious to cardiac tissue than normal ad lib.-fed diet. In conclusion, the effects of caloric restriction on myocardial oxidative stress is dependent on which nutrient is restricted. Dietary restriction of fatty acid-enriched diets is deleterious relative to ad lib.-fed chow diet. (C) 2002 Elsevier, Science Ltd. All rights reserved.

Beta-carotene supplementation attenuates cardiac remodeling induced by one-month tobacco-smoke exposure in rats

Objective: the objectives were to analyze the cardiac effects of exposure to tobacco smoke (ETS), for a period of 30 days, alone and in combination with beta-carotene supplementation (BC). Research methods and procedures: Rats were allocated into: Air (control, n = 13); Air + BC (n = 11); ETS (n = 11); and BC + ETS (n = 9). In Air + BC and BC + ETS, 500 mg of BC were added to the diet. After three months of randomization, cardiac structure and function were assessed by echocardiogram. After that, animals were euthanized and morphological data were analyzed post-morten. One-way and two-way ANOVA were used to assess the effects of ETS, BC and the interaction between ETS and BC on the variables. Results: ETS presented smaller cardiac output (0.087 +/- 0.001 vs. 0.105 +/- 0.004 l/min; p = 0.007), higher left ventricular diastolic diameter (19.6 +/- 0.5 vs. 18.0 +/- 0.5 mm/kg; p = 0.024), higher left ventricular (2.02 +/- 0.05 vs. 1.70 +/- 0.03 g/kg; p < 0.001) and atrium (0.24 +/- 0.01 vs. 0.19 +/- 0.01 g/kg; p = 0.003) weight, adjusted to body weight of animals, and higher values of hepatic lipid hydroperoxide (5.32 +/- 0.1 vs. 4.84 +/- 0.1 nmol/g tissue; p = 0.031) than Air. However, considering those variables, there were no differences between Air and BC + ETS (0.099 +/- 0.004 l/min; 19.0 +/- 0.5 mm/kg; 1.83 +/- 0.04 g/kg; 0.19 +/- 0.01 g/kg; 4.88 +/- 0.1 nmol/g tissue, respectively; p > 0.05). Ultrastructural alterations were found in ETS: disorganization or loss of myofilaments, plasmatic membrane infolding, sarcoplasm reticulum dilatation, polymorphic mitochondria with swelling and decreased cristae. In BC + ETS, most fibers showed normal morphological aspects. Conclusion: One-month tobacco-smoke exposure induces functional and morphological cardiac alterations and BC supplementation attenuates this ventricular remodeling process.

The influence of temporal food restriction on the performance of isolated cardiac muscle

In this study we assessed the mechanical function of isolated left ventricular papillary muscles from 60 day-old male Wistar-Kyoto rats (WKY) subjected to different periods of food restriction (FR). The food-restricted animals (R) were fed 50% of the amount of diet consumed by the ad Libitum-fed rats (C). The cardiac muscles were studied after 30, 60, and 90 days (R-30, R-60 and R-90) of FR. The effect of FR on myocardial collagen concentration was also evaluated. The parameters from the three control groups that were statistically identical were combined and the control pool group (CP) was formed. The left ventricular weight-to-body weight ratio was lower in the R-30 and higher in the R-60 and R-90 in relation to their control groups. Hydroxyproline concentration was higher only in R-90 compared to CP and R-30. Myocardial mechanical function was the same in the C groups. The comparisons between CP and FR groups showed that: the muscles of R-30 presented increased resting tension and maximum rate of tension decline, and decreased velocity of shortening; the muscles of R-60 and R-90 groups showed a prolongation of the time to peak tension (TPT) and the time to peak shortening (TPS); and R-30 had an increased time from peak tension to 50% relaxation (RT1/2). Increases in TPT, TPS, and RT1/2 in groups R-60 and R-90 were significant in relation to R-30. In conclusion, while FR for 30 days produces disparate effects on myocardial performance, FR for 60 and 90 days prolongs the contraction period. The change of relaxation time in R-90 might be related to the increased myocardial collagen content. (C) 2001 Elsevier B.V. All rights reserved.

Follow-up study of morphology and cardiac function in rats undergoing induction of supravalvular aortic stenosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

OBJECTIVE: To assess the effect of food restriction (FR) on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR). METHODS: Isolated papillary muscle preparations of the left ventricle (LV) of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY) rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet) for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1) reduction in the body weight and LV weight of SHR and WKY rats; 2) increase in the time to peak shortening and the time to peak developed tension (DT) in the hypertrophied myocardium of the SHR; 3) diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats

Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5 mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4 ma/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo 111). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p < 0.01). Lycopene levels (mean +/- S.D. nmol/kg) in saponified hearts were similar between L (47.43 +/- 11.78) and DL (49.85 +/- 16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage. (c) 2007 Elsevier B.V. All rights reserved.

Alternative pathways for catecholamine action in oral motor control

Orofacial movement is a complex function performed by facial and jaw muscles. Jaw movement is enacted through the triggering of motoneurons located primarily in the trigeminal motor nucleus (Mo5). The Mo5 is located in the pontine reticular formation, which is encircled by premotor neurons. Previous studies using retrograde tracers have demonstrated that premotor neurons innervating the Mo5 are distributed in brainstem areas, and electrophysiological studies have suggested the existence of a subcortical relay in the corticofugal-Mo5 pathway. Various neurotransmitters have been implicated in oral movement. Dopamine is of special interest since its imbalance may produce changes in basal ganglia activity, which generates abnormal movements, including jaw motor dysfunction, as in oral dyskinesia and possibly in bruxism. However, the anatomical pathways connecting the dopaminergic systems with Mo5 motoneurons have not been studied systematically. After injecting retrograde tracer fluorogold into the Mo5, we observed retrograde-labeled neurons in brainstem areas and in a few forebrain nuclei, such as the central nucleus of the amygdala, and the parasubthalamic nucleus. By using dual-labeled immunohistochemistry, we found tyrosine hydroxylase (a catecholamine-processing enzyme) immunoreactive fibers in close apposition to retrograde-labeled neurons in brainstem nuclei, in the central nucleus of the amygdala and the parasubthalamic nucleus, suggesting the occurrence of synaptic contacts. Therefore, we suggested that catecholamines may regulate oralfacial movements through the premotor brainstem nuclei, which are related to masticatory control, and forebrain areas related to autonomic and stress responses. (C) 2005 Elsevier B.V.. All rights reserved.

Important GABAergic mechanism within the NTS and the control of sympathetic baroreflex in SHR

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diet-induced obesity causes metabolic, endocrine and cardiac alterations in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiac remodeling in a rat model of diet-induced obesity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Atrophic Cardiac Remodeling Induced by Taurine Deficiency in Wistar Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of Taurine on Cardiac Remodeling Induced by Tobacco Smoke Exposure

Background/Aims: To investigate the effect of taurine on cardiac remodeling induced by smoking. Methods: In the first step, rats were allocated into two groups: Group C (n=14): control; Group T (n=14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n=9): rats exposed to tobacco smoke; Group ETS-T (n=9): rats exposed to tobacco smoke and treated with taurine for two months. Results: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. on the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS=1.30 (1.20-1.42); ETS-T=1.50 (1.40-1.50); p=0.029), E/A ratio (ETS=1.13 +/- 0.13; ETS-T=1.37 +/- 0.26; p=0.028), and isovolumetric relaxation time normalized for heart rate (ETS=53.9 +/- 4.33; ETS-T=72.5 +/- 12.0; p<0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS=204 +/- 14 nmol/mg protein; ETS-T=232 +/- 12 nmol/mg protein; p<0.001). ETS-T group presented lower levels of phospholamban (ETS=1.00 +/- 0.13; ETS-T=0.82 +/- 0.06; p=0.026), phosphorylated phospholamban at Ser16 (ETS=1.00 +/- 0.14;ETS-T=0.63 +/- 0.10;p=0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS=1.01 +/- 0.17; ETS-T=0.77 +/- 0.11; p=0.050). Conclusion: In normal rats, taurine produces no effects on cardiac morphological or functional variables. on the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism. Copyright (C) 2011 S. Karger AG, Basel

Influence of different doses of retinoic acid on cardiac remodeling

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)