Mechanisms involved in cardiac function and calcium (Ca.sup.2+) handling in obese-resistant (OR) rats are still poorly determined. We tested the hypothesis that unsaturated high-fat diet (HFD) ...promotes myocardial dysfunction in OR rats, which it is related to Ca.sup.2+ handling. In addition, we questioned whether exercise training (ET) becomes a therapeutic strategy. Male Wistar rats (n=80) were randomized to standard or HFD diets for 20 weeks. The rats were redistributed for the absence or presence of ET and OR: control (C; n=12), control + ET (CET; n=14), obese-resistant (OR; n=9), and obese-resistant + ET (ORET; n=10). Trained rats were subjected to aerobic training protocol with progressive intensity (55-70% of the maximum running speed) and duration (15 to 60 min/day) for 12 weeks. Nutritional, metabolic, and cardiovascular parameters were determined. Cardiac function and Ca.sup.2+ handling tests were performed in isolated left ventricle (LV) papillary muscle. OR rats showed cardiac atrophy with reduced collagen levels, but there was myocardial dysfunction. ET was efficient in improving most parameters of body composition. However, the mechanical properties and Ca.sup.2+ handling from isolated papillary muscle were similar among groups. Aerobic ET does not promote morphological and cardiac functional adaptation under the condition of OR. Key words: High-fat diet; Obesity; Resistance to obesity; Exercise training; Myocardial function; Calcium handling
Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and sarcolemmal Na+/Ca2+ exchanger (NCX1) structures are involved in heart cell Ca2+ homeostasis. Previous studies have shown discrepancies in their ...function and expression in heart failure. The goal of this study was to evaluate heart function and hypertrophied muscle Ca2+-handling protein behavior under pressure overload. Twenty male Wistar rats were divided into two groups: Aortic stenosis (AoS), induced by a clip placed at the beginning of the aorta, and Control (Sham). After 18 weeks, heart function and structure were evaluated by echocardiogram. Myocardial function was analyzed by isolated papillary muscle (IPM) at basal condition and Ca2+ protein functions were evaluated after post-pause contraction and blockage with cyclopiazonic acid in IPM. Ca2+-handling protein expression was studied by western blot (WB). Echocardiogram showed that AoS caused concentric hypertrophy with enhanced ejection fraction and diastolic dysfunction inferred by dilated left atrium and increased relative wall thickness. IPM study showed developed tension was the same in both groups. AoS showed increased stiffness revealed by enhanced resting tension, and changes in Ca2+ homeostasis shown by calcium elevation and SERCA2a blockage maneuvers. WB revealed decreased NCX1, SERCA2a, and phosphorylated phospholambam (PLB) on serine-16 in AoS. AoS had left ventricular hypertrophy and diastolic dysfunction compared to Sham; this could be related to our findings regarding calcium homeostasis behavior: deficit in NCX1, SERCA2a, and phosphorylated PLB on serine-16.
Obesity is often associated with changes in cardiac function; however, the mechanisms responsible for functional abnormalities have not yet been fully clarified. Considering the lack of information ...regarding high-saturated-fat diet-induced obesity, heart function, and the proteins involved in myocardial calcium (Ca2+) handling, the aim of this study was to test the hypothesis that this dietary model of obesity leads to cardiac dysfunction resulting from alterations in the regulatory proteins of intracellular Ca2+ homeostasis. Male Wistar rats were distributed into two groups: control (C, n=18; standard diet) and obese (Ob, n=19; high-saturated-fat diet), which were fed for 33 weeks. Cardiac structure and function were evaluated using echocardiographic and isolated papillary muscle analyses. Myocardial protein expressions of sarcoplasmic reticulum Ca2+-ATPase, phospholamban (PLB), PLB serine-16 phosphorylation, PLB threonine-17 phosphorylation, ryanodine receptor, calsequestrin, Na+/Ca2+ exchanger, and L-type Ca2+ channel were assessed by western blot. Obese rats presented 104% increase in the adiposity index (C: 4.5±1.4 vs Ob: 9.2±1.5%) and obesity-related comorbidities compared to control rats. The left atrium diameter (C: 5.0±0.4 vs Ob: 5.5±0.5 mm) and posterior wall shortening velocity (C: 36.7±3.4 vs Ob: 41.8±3.8 mm/s) were higher in the obese group than in the control. The papillary muscle function was similar between the groups at baseline and after inotropic and lusitropic maneuvers. Obesity did not lead to changes in myocardial Ca2+ handling proteins expression. In conclusion, the hypothesis was not confirmed, since the high-saturated-fat diet-induced obese rats did not present cardiac dysfunction or impaired intracellular Ca2+ handling proteins.
Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, ...is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats.
Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test.
Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups.
Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study was undertaken to determine anthropometrical parameters in male adult Wistar rats. We tested the hypothesis that the anthropometrical index may identify obesity and may predict its ...adverse effects on lipid profile and oxidative stress in rats. Two experimental protocols were performed. In the first experiment, 50 male Wistar rats, 21 days old and fed a control chow were studied up to 150 days of age. In the second experiment, male Wistar rats, 60 days old, were divided into three groups (n = 8): control (C) given free access to a control chow; (S) receiving the control chow and drinking 30% sucrose ad libitum and (HC) fed a high-carbohydrate diet ad libitum. The first experiment showed that food consumption, energy intake and body weight increased with increasing age, while specific rate of body mass gain was significantly decreased. There were no significant differences in body length and thoracic circumference of rats from 60 days of age. The abdominal circumference (AC) and body mass index (BMI) significantly increased with enhancing age in rats up to 90 days of age and remained constant thereafter. In the second experiment, after 30 days of dietary treatment, the final body weight, body mass gain, carcass fat and BMI were higher in S and HC rats than in C. There were no significant alterations in body length and carcass protein among the groups. Triacylglycerol (TG), total cholesterol (CT), low-density lipoprotein cholesterol (LDL-C) and lipid hydroperoxide (LH) were higher in S and HC rats than in C. High-density lipoprotein cholesterol (HDL-C) decreased in HC rats and total antioxidant substances (TAS) decreased in S and HC rats. There were positive correlations between BMI with carcass fat, BMI with LH and BMI and serum TG concentration. In conclusion, the BMI for male adult Wistar rats ranged between 0.45 and 0.68 g/cm2. Obesity may be easily estimated from the BMI in rats. Alterations in BMI were associated with dyslipidemic profile and oxidative stress in serum of rats and BMI may predict these adverse consequences of the obesity in rats.
In experimental studies, several parameters, such as body weight, body mass index, adiposity index, and dual-energy X-ray absorptiometry, have commonly been used to demonstrate increased adiposity ...and investigate the mechanisms underlying obesity and sedentary lifestyles. However, these investigations have not classified the degree of adiposity nor defined adiposity categories for rats, such as normal, overweight, and obese. The aim of the study was to characterize the degree of adiposity in rats fed a high-fat diet using cluster analysis and to create adiposity intervals in an experimental model of obesity. Thirty-day-old male Wistar rats were fed a normal (n=41) or a high-fat (n=43) diet for 15 weeks. Obesity was defined based on the adiposity index; and the degree of adiposity was evaluated using cluster analysis. Cluster analysis allowed the rats to be classified into two groups (overweight and obese). The obese group displayed significantly higher total body fat and a higher adiposity index compared with those of the overweight group. No differences in systolic blood pressure or nonesterified fatty acid, glucose, total cholesterol, or triglyceride levels were observed between the obese and overweight groups. The adiposity index of the obese group was positively correlated with final body weight, total body fat, and leptin levels. Despite the classification of sedentary rats into overweight and obese groups, it was not possible to identify differences in the comorbidities between the two groups.
Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a ...known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group.
Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of ...antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM).
Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney.
Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups.
Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control ...(C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73±0.49; C-Ex: 5.67±0.53; DM-Sed: 6.41±0.54; DM-Ex: 5.81±0.50 mm; P<0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. Conclusion. Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.
Abstract Aldosterone plays a pivotal role in the pathophysiology of systolic heart failure. However, whether early aldosterone antagonism improves cardiac remodeling during persistent pressure ...overload is unsettled. We evaluated the effects of aldosterone antagonist spironolactone on cardiac remodeling in rats with ascending aortic stenosis (AS). Methods Three days after inducing AS, weaning rats were randomized to receive spironolactone (AS-SPR, 20 mg/kg/day) or no drug (AS) for 18 weeks, and compared with sham-operated rats. Myocardial function was studied in isolated left ventricular (LV) papillary muscles. Statistical analyses: ANOVA or Kruskal–Wallis tests. Results Echocardiogram showed that LV diastolic (Sham 8.73 ± 0.57; AS 8.30 ± 1.10; AS-SPR 9.19 ± 1.15 mm) and systolic (Sham 4.57 ± 0.67; AS 3.61 ± 1.49; AS-SPR 4.62 ± 1.48 mm) diameters, left atrial diameter (Sham 5.80 ± 0.44; AS 7.15 ± 1.22; AS-SPR 8.02 ± 1.17 mm), and LV mass were higher in AS-SPR than AS. Posterior wall shortening velocity (Sham 38.5 ± 3.8; AS 35.6 ± 5.6; AS-SPR 31.1 ± 3.8 mm/s) was lower in AS-SPR than Sham and AS; E/A ratio was higher in AS-SPR than Sham. Developed tension was lower in AS and AS-SPR than Sham. Time to peak tension was higher in AS-SPR than Sham and AS after post-rest contraction. Right ventricle weight was higher in AS-SPR than AS, suggesting more severe heart failure in AS-SPR than AS. Interstitial collagen fractional area and myocardial hydroxyproline concentration were higher in AS than Sham. Metalloproteinase-2 and -9 activity, evaluated by zymography, did not differ between groups. Conclusion Early spironolactone administration causes further hypertrophy in cardiac chambers, and left ventricular dilation and dysfunction in rats with AS-induced chronic pressure overload.
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