Divanei Zaniqueli

Long-term use of low-dose spironolactone in spontaneously hypertensive rats: Effects on left ventricular hypertrophy and stiffness

The aim of the present study was to evaluate the effect of low-dose spironolactone initiated during the early stages of hypertension development and to assess the effects of chronic pressure overload on ventricular remodeling in rats. Male spontaneously hypertensive rats (SHRs) (4 weeks) were randomized to receive daily spironolactone (20 mg/kg) or vehicle (mineral oil) from 4 weeks to 8 months of age. Systolic blood pressure was measured non-invasively by tail-cuff pletysmography at baseline, 4 and 8 months. Hemodynamic assessment was performed at the end of treatment by arterial and ventricular catheterization. An in situ left ventricular pressure-volume curve was created to evaluate dilatation and wall stiffness. Systolic blood pressure at 1 month of age was higher in SHRs than in the Wistar group; it increased throughout the follow-up period and remained elevated with treatment (Wistar: 136 ± 2, SHR: 197 ± 6.8, SHR-Spiro: 207 ± 7.1 mmHg; p < 0.05). Spironolactone reduced cardiac hypertrophy (Wistar: 1.25 ± 0.03 SHR: 1.00 ± 0.03, SHR-Spiro: 0.86 ± 0.02 g; p < 0.05) and left ventricular mass normalized to body weight (Wistar: 2.51 ± 0.06, SHR: 2.70 ± 0.08, 2.53 ± 0.07 mg/g; p < 0.05). Moreover, the left ventricular wall stiffness that was higher in SHRs was partially reduced by spironolactone treatment (Wistar: 0.370 ± 0.032; SHR: 0.825 ± 0.058; SHR-Spiro: 0.650 ± 0.023 mmHg/ml; p < 0.05). Our results show that long-term spironolactone treatment initiated at the early stage of hypertension development reduces left ventricular hypertrophy and wall stiffness in SHRs.

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

OBJECTIVE: To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake. INTRODUCTION: High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system. METHODS: Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg-1) (SHR-Salt-S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves. RESULTS: The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar  =  109±2; SHR  =  118±2; SHR-Salt  =  117±2; SHR-Salt-S  =  116±2 mmHg; P<0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar  =  2.90±0.06; SHR  =  3.44±0.07; SHR-Salt  =  3.68±0.07; SHR-Salt-S  =  3.46±0.05 mg/g; P<0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar  =  -3698±92; SHR  =  -3729±125; SHR-Salt  =  -3342±80; SHR-Salt-S  =  -3647±104 mmHg/s; P<0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar  =  1.40±0.04; SHR  =  1.60±0.05; SHR-Salt  =  1.67±0.12; SHR-Salt-S  =  1.45±0.03 mmHg/ml; P<0.05). CONCLUSION: Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.

Carvedilol recovers normal blood pressure variability in rats with myocardial infarction

BACKGROUND The aim of this study was to investigate the effects of chronic treatment with carvedilol in blood pressure (BPV) and heart rate (HRV) variability of rats with myocardial infarction (MI). METHODS MI was produced in male rats by ligature of anterior interventricular branch of left coronary artery. Control rats were submitted to a sham surgery (SO). MI and SO rats were randomized to receive for 30 days placebo (Plac 0.5% metilcelulose) or carvedilol (Carv, 2mg/Kg body weight/day, drinking water): SO-Plac (N = 10), SO-Carv (N = 10), MI-Plac (N = 12), MI-Carv (N = 13). Blood pressure (BP) was directly recorded in the awake animals and BPV was determined, in time (variance, mmhg(2)) and frequency domains by the autoregressive method. Statistical significance was set in P<0.05. Data are median and interquartile range. RESULTS No significant changes in HRV was observed in MI rats, while BPV showed significant decreasing of blood pressure variance (SO-Plac = 42.08 (39.21) mmHg(2) vs. MI-Plac = 21.67 (12.58) mmHg(2), P<0.05), reversed by the Carv treatment (MI-Plac = 21.67 (12.58) vs. MI-Carv = 38.64 (29.25), P<0.05). In the frequency domain analyses, MI reduced absolute and normalized LF component (LF (mmHg(2)): SO-Plac = 8.98 (14.84) vs. MI-Plac = 2.08 (4.84), P<0.05; LF(nu): SO-Plac = 79.48 (45.03) nu vs. MI-Plac = 24.25 (40.67) nu, P<0.05) and increased the normalized HF component of the BPV (SO-Plac = 20.51 (39.18) vs. MI-Plac = 60.51 (39.73). Carv treatment significantly attenuated the LF component fall. CONCLUSION Chronic treatment with carvedilol restored the variance of BPV altered by the MI.

Long-term intense resistance training in men is associated with preserved cardiac structure/function, decreased aortic stiffness, and lower central augmentation pressure.

Objective: There have been contradictory reports regarding resistance exercise and central arterial compliance. The American Heart Association has recommended its use in preventing/treating cardiovascular diseases. We examined the effects of long-term endurance running and intense resistance training on central hemodynamics, compared with healthy control (CON). Methods: Sixty-nine male participants, 25–50 years [19 intense resistance trained (IRT) group, 21 endurance runners, and 29 CON] were investigated by radial tonometry-pulse wave analysis, pulse wave velocity (PWV), and echocardiogram. Data were expressed as mean ± SE (median). Differences were tested by analysis of variance and analysis of covariance was used to adjust for confounding variables. Results: There were no differences among groups regarding age, height (Ht), brachial and central blood pressure. Resting heart rate (HR) was lower and high-density lipoprotein cholesterol (HDL-C) higher in endurance runners. Weight, peripheral pulse pressure, and pulse pressure amplification were higher and HDL-C lower in the IRT group. Left ventricular mass and creatine phosphokinase were higher in trained participants. Relative wall thickness was similar among groups. The ratio of the velocity of peak E and A waves (E/A) was higher and PWV significantly lower in endurance runners (7.2 ± 0.14 m/s) and IRT (7.5 ± 0.14 m/s) as compared with CON (8.2 ± 0.16 m/s) even after adjustments for age, Ht, HR and mean arterial pressure (MAP), or mean systolic pressure. Differences in central augmentation pressure (cAP) adjusted for age, height, systolic or MAP, PWV, and HR (IRT equal to 0.08 ± 0.9, CON equal to 3.4 ± 0.9 and endurance running equal to 3.6 ± 1) were no longer significant after further adjustments to aortic diameter or weight. Conclusion: Long-term resistance training in men is associated with preserved cardiac structure/function, decreased aortic stiffness, and lower cAP.

Heart rate at 4 s after the onset of exercise in endurance-trained men

It has been suggested that the increase in heart rate (HR) at the onset of exercise is caused by vagal withdrawal. In fact, endurance runners show a lower HR in maximum aerobic tests. However, it is still unknown whether endurance runners have a lower HR at 4 s after the onset of exercise (4th-sec-HR). We sought to measure the HR at the onset of the 4 s exercise test (4-sET), clarifying its relationship to heart rate variability (HRV), spectral indices, and cardiac vagal index (CVI) in endurance runners (ER) and healthy untrained controls (CON). HR at 4th-sec-HR, CVI, and percent HR increase during exercise were analyzed in the 4-sET. High frequency spectrum (HF-nu), low frequency spectrum (LF-nu), and low frequency/high frequency band ratio (LF/HF) were analyzed from the HRV. ER showed a significantly higher HF, and both a lower LF and LF/HF ratio compared with the CON. ER presented a significantly lower 4th-sec-HR, although neither CVI nor HR increases during exercise were statistically different from the CON. In conclusion, ER presented a lower 4th-sec-HR secondary to increased vagal influence over the sinus node. CVI seems to be too weak to use for discriminating individuals with respect to the magnitude of HR vagal control.

Gender-specific determinants of blood pressure elevation in Angolan adults

Abstract Background: Hypertension affects African–American adults more than any other ethnic group in the US. However, some of the black populations living outside Africa are well adapted to food and lifestyle. We aimed to describe the clinical characteristics underlying the gender-specific determinants of BP and the risk of hypertension in public-sector workers living in Angola. Materials and methods: 609 volunteers (48% men) were included in this cross-sectional and descriptive study. Demographic, socioeconomic and life style data were collected during an interview. Systolic BP (SBP) and diastolic BP (DBP) were measured, along with some anthropometric and clinical variables. Results: The prevalence of hypertension is 45.2% without difference between genders. Obesity was more prevalent in women (29.2% vs. 8.9%, p < 0.05). The age-related increment in SBP is higher in women (14.2 ± 1.1 vs 9.5 ± 1.3 mmHg/decade, p < 0.05). In men, age, BMI, cholesterol and LDLc/HDLc explained 21, 4, 2.5 and 2.9% of SBP variability, respectively. In women, age, BMI and HC explain 27, 2 and 1% of SBP variability, respectively. The risk for hypertension is 5 × high among men aged ≥45 years, and 3.5× in those having BMI ≥25. Women aged 45 years or older have 8 × risk of hypertension and 2× the risk by having BMI ≥25. Conclusions: We found that advanced age (≥45) and overweight/obesity (BMI ≥25) are the main risk factors for hypertension in adults from Angola. However, our data suggest that age and BMI may have different influence on increasing BP in men and women.

Early sex differences in central arterial wave reflection are mediated by different timing of forward and reflected pressure waves

Non‐invasive assessment of central arterial pulse wave augmentation has been proved to be useful in predicting cardiovascular adverse events. Previous studies have shown that pre‐pubescent girls had greater central augmentation pressure compared with height‐matched boys. This study sought to investigate which factors contribute to the body height‐independent sexual differences in central arterial wave reflection observed in childhood. This cross‐sectional study involved 819 children and adolescents (6‐18 years of age) of both sexes. Phenotypes of central haemodynamic were obtained by radial applanation tonometry. Heart rate corrected augmentation index (Aix@75) was greater in girls compared with boys (2.9 ± 10.7 vs −1.7 ± 12.9%, P < .001) as well as the central augmented pressure (cAP; 1.3 ± 3.3 vs 0.1 ± 3.8 mm Hg, P < .001), even adjusting for age, heart rate and body height. Left ventricular ejection duration (ED) was longer (320 ± 26 vs 314 ± 24 ms, P = .004) and time to inflection point (Tr) was shorter in girls (139 ± 14 vs 141 ± 21 ms, P = .014). The reduction of Aix@75 with increasing body height was steeper in boys (−0.499 ± 0.030 vs −0.428 ± 0.036%/cm, P < .001) as well as the reduction of cAP with increasing body height (−0.108 ± 0.010 vs −0.066 ± 0.013 mm Hg/cm, P < .001). Body height‐independent sexual differences observed in the pulse wave reflection indices from early adolescence were mediated by different timing of forward and reflected pressure waves.

Body fat percentage is better than indicators of weight status to identify children and adolescents with unfavorable lipid profile

OBJECTIVE To assess whether the indicators of weight status body mass index and waist-to-height ratio are similar to body fat percentage to identify obese children and adolescents with unfavorable lipid profile. METHODS This was a cross-sectional study involving 840 children and adolescents (6-18 years). The same individuals were classified as non-obese (<P95) or obese (≥P95) according to body fat percentage and indicators of weight status, body mass index, and waist-to-height ratio. Body fat percentage was obtained by multi-frequency bioelectrical impedance. Linear association between obesity and increased lipid fractions was tested by ANCOVA. Normal distribution curves of non-HDL cholesterol were designed for obese and non-obese. To provide the proportion of obese individuals with elevated non-HDL-c across all indicators, Z-score was calculated. RESULTS Obese boys presented higher non-HDL cholesterol when compared with those non-obese, classified by body mass index (107±28 vs. 94±25mg/dL, p=0.001), waist-to-height ratio (115±29 vs. 94±25mg/dL, p<0.001) and body fat percentage (119±33 vs. 94±24mg/dL, p<0.001). Differently, obese girls presented with higher non-HDL cholesterol when compared with those non-obese only according to the body fat percentage classification (118±24 vs. 96±26mg/dL, p=0.001). A large shift to the right in the distribution curve of non-HDL cholesterol among obese girls compared with non-obese was observed only when body fat percentage was used to discriminate between obese and non-obese. CONCLUSION Body fat percentage was better than the indicators of weight status to identify children and adolescents with unfavorable lipid profile, mainly among girls.

Waist-to-height ratio is as reliable as biochemical markers to discriminate pediatric insulin resistance

OBJECTIVE Given the importance of incorporating simple and low-cost tools into the pediatric clinical setting to provide screening for insulin resistance, the present study sought to investigate whether waist-to-height ratio is comparable to biochemical markers for the discrimination of insulin resistance in children and adolescents. METHODS This cross-sectional study involved students from nine public schools. In total, 296 children and adolescents of both sexes, aged 8-14 years, composed the sample. Waist-to-height ratio, triglycerides/glucose index, and triglycerides-to-HDL-C ratio were determined according to standard protocols. Insulin resistance was defined as homeostatic model assessment for insulin resistance with cut-off point ≥3.16. RESULTS Age, body mass index, frequency of overweight, waist circumference, waist-to-height ratio, insulin, glucose, homeostatic model assessment for insulin resistance, triglycerides, triglycerides/glucose index, and triglycerides-to-HDL-C were higher among insulin-resistant boys and girls. Moderate correlation of all indicators (waist-to-height ratio, triglycerides/glucose index, and triglycerides-to-HDL-C ratio) with homeostatic model assessment for insulin resistance was observed for both sexes. The areas under the receiver operational characteristic curves were similar between waist-to-height ratio and biochemical markers. CONCLUSION The indicators provided similar discriminatory power for insulin resistance. However, taking into account the cost-benefit ratio, the authors suggest that waist-to-height ratio may be a useful tool to provide screening for insulin resistance in pediatric populations.

Excess weight in children and adolescents is associated with altered subendocardial blood supply among girls but not boys

Subendocardial viability ratio (SEVR) is a reliable index of myocardial supply‐workload balance. This study sought to investigate whether overweight/obese children and adolescents have altered SEVR and to identify which are the associated factors. This cross‐sectional study involved 789 individuals. Central haemodynamic was measured by radial applanation tonometry. Diastolic time was shorter (496 ± 122 vs 537 ± 140 ms, P = .014) and diastolic pressure‐time index was lower (2681 ± 412 vs 2814 ± 423 mm Hg seconds, P = .024) in overweight/obese compared with eutrophic girls. SEVR was lower in girls than in boys (1.34 ± 0.39 vs 1.48 ± 0.41, P = .018) but only among overweight/obese. SEVR may be affected by small variations in the temporal determinants of cardiac cycle.