Multiple mechanisms act to maintain kidney oxygenation during renal ischemia in anesthetized rabbits.

We examined the mechanisms that maintain stable renal tissue PO(2) during moderate renal ischemia, when changes in renal oxygen delivery (DO(2)) and consumption (VO(2)) are mismatched. When renal artery pressure (RAP) was reduced progressively from 80 to 40 mmHg, VO(2) (-38 ± 7%) was reduced more than DO(2) (-26 ± 4%). Electrical stimulation of the renal nerves (RNS) reduced DO(2) (-49 ± 4% at 2 Hz) more than VO(2) (-30 ± 7% at 2 Hz). Renal arterial infusion of angiotensin II reduced DO(2) (-38 ± 3%) but not VO(2) (+10 ± 10%). Despite mismatched changes in DO(2) and VO(2), renal tissue PO(2) remained remarkably stable at ≥40 mmHg RAP, during RNS at ≤2 Hz, and during angiotensin II infusion. The ratio of sodium reabsorption to VO(2) was reduced by all three ischemic stimuli. None of the stimuli significantly altered the gradients in PCO(2) or pH across the kidney. Fractional oxygen extraction increased and renal venous PO(2) fell during 2-Hz RNS and angiotensin II infusion, but not when RAP was reduced to 40 mmHg. Thus reduced renal VO(2) can help prevent tissue hypoxia during mild renal ischemia, but when renal VO(2) is reduced less than DO(2), other mechanisms prevent a fall in renal PO(2). These mechanisms do not include increased efficiency of renal oxygen utilization for sodium reabsorption or reduced washout of carbon dioxide from the kidney, leading to increased oxygen extraction. However, increased oxygen extraction could be driven by altered countercurrent exchange of carbon dioxide and/or oxygen between renal arteries and veins.

Acculturation and self-reported health among Hispanics using a socio-behavioral model: the North Texas Healthy Heart Study.

BACKGROUND: Acculturation is a continuous, firsthand contact with other cultures functioning at both group and individual levels and is reflected in our culturally diverse society, calling for a greater understanding of the environmental and cultural impact on health. Self-reported health (SRH), a robust and well validated predictor of future mortality for all racial/ethnic groups, has been differentially reported by Hispanics compared to whites, especially based on their acculturation status. This study investigated the relationship between acculturation and SRH among Hispanics. An adapted Andersen framework was used to develop logistic regression models to assess for an association between acculturation and general health status. METHODS: Hispanic participants (n = 135), as part of the North Texas Healthy Heart Study, were administered standardized questionnaires on acculturation, psychosocial measures which included sense of control, stress, depression and social support and a single item SRH measure. In addition, physiological measurements and demographic characteristics including age, gender, body mass index, medical history, and socioeconomic status were also obtained. RESULTS: Bivariate analyses found Mexican-oriented participants 3.16 times more likely to report fair/poor SRH compared to Anglo-oriented Hispanics. Acculturation was also associated with SRH in multiple regression models controlling for enabling, need, and predisposing factors together (OR: 3.53, 95% CI: 1.04, 11.97). CONCLUSIONS: Acculturation status was associated with SRH after accounting for other underlying factors. Medical and public health professionals should promote the use of acculturation measures in order to better understand its role in Hispanic behaviors, health outcomes and health care use. Such research findings will contribute to the design of culturally sensitive prevention and treatment strategies for diverse and immigrant populations.

Altered responsiveness of the kidney to activation of the renal nerves in fat-fed rabbits.

We tested whether mild adiposity alters responsiveness of the kidney to activation of the renal sympathetic nerves. After rabbits were fed a high-fat or control diet for 9 wk, responses to reflex activation of renal sympathetic nerve activity (RSNA) with hypoxia and electrical stimulation of the renal nerves (RNS) were examined under pentobarbital anesthesia. Fat pad mass and body weight were, respectively, 74% and 6% greater in fat-fed rabbits than controls. RNS produced frequency-dependent reductions in renal blood flow, cortical and medullary perfusion, glomerular filtration rate, urine flow, and sodium excretion and increased renal plasma renin activity (PRA) overflow. Responses of sodium excretion and medullary perfusion were significantly enhanced by fat feeding. For example, 1 Hz RNS reduced sodium excretion by 79 +/- 4% in fat-fed rabbits and 46 +/- 13% in controls. RNS (2 Hz) reduced medullary perfusion by 38 +/- 11% in fat-fed rabbits and 9 +/- 4% in controls. Hypoxia doubled RSNA, increased renal PRA overflow and medullary perfusion, and reduced urine flow and sodium excretion, without significantly altering mean arterial pressure (MAP) or cortical perfusion. These effects were indistinguishable in fat-fed and control rabbits. Neither MAP nor PRA were significantly greater in conscious fat-fed than control rabbits. These observations suggest that mild excess adiposity can augment the antinatriuretic response to renal nerve activation by RNS, possibly through altered neural control of medullary perfusion. Thus, sodium retention in obesity might be driven not only by increased RSNA, but also by increased responsiveness of the kidney to RSNA.

Impact of race/ethnicity on the relationship between visceral fat and inflammatory biomarkers.

The purpose of this study was to determine whether racial/ethnic differences exist in the relationship between visceral adipose tissue (VAT) and selected inflammatory biomarkers. Subjects included 136 African-American, 133 Hispanic, and 100 white men and women, aged > or =45. Waist circumference and BMI were measured using standard methods. Total VAT, and VAT and subcutaneous adipose tissue (SAT) at the L4L5 spinal level were measured using computed tomography. Interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen were measured from fasting blood samples. Results revealed that waist circumference and BMI were similar among groups but African Americans had significantly lower L4L5 VAT compared with Hispanics and whites. Despite lower VAT, African-American men had similar concentrations of inflammatory biomarkers. On the other hand, African-American women had higher CRP and IL-6 than white women, and higher fibrinogen than both Hispanic and white women. After controlling for L4L5 VAT, L4L5 SAT, and age, African-American women had higher concentrations of IL-6 and fibrinogen. Stratified analyses for CRP indicated that L4L5 SAT was associated with CRP in African-American and white women after controlling for L4L5 VAT and age, but that the reverse was not true. These data indicate that African Americans had lower VAT but similar or higher concentrations of inflammatory biomarkers. African-American women consistently displayed greater inflammation compared with whites, even after controlling for VAT or SAT.

Visceral adipose tissue loss and insulin resistance 6 months after laparoscopic gastric banding surgery: a preliminary study.

BACKGROUND: Increased visceral adipose tissue (VAT) is thought to be a risk factor for cardiovascular and metabolic diseases. There are only limited data on whether VAT loss after laparoscopic gastric banding surgery (LGBS) is related to risk factor reduction. This study determined whether improvements in risk markers, in particular insulin resistance, were related to VAT reduction at 6 months after LGBS (T2). METHODS: Thirty-four LGBS patients and 17 normal weight controls underwent initial and T2 testing. Fasting venous blood samples were taken to evaluate glucose, insulin, hemoglobin A(1c), lipids, C-reactive protein (CRP), and hormone profiles. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. VAT was measured using CT techniques. Data were analyzed using repeated measures ANOVA and regression analysis. RESULTS: Results at T2 showed that patients had significant improvements in body composition, HOMA, and hemoglobin A(1c). There were also reductions in plasma renin activity and leptin, and increases in ghrelin and GLP-1. Reductions in VAT were significantly correlated with reductions in insulin, HOMA, and glucose. While high density lipoprotein cholesterol, triglycerides, CRP, and the apolipoprotein A1/B ratio were also improved, VAT reduction was significantly correlated only with an increased apolipoprotein A1/B ratio. CONCLUSION: These data indicate that 6 months after LGBS there were significant improvements in many cardiovascular and metabolic risk markers. However, VAT reduction was most strongly associated with reductions in insulin resistance. Body weight loss was not associated with markers of improved insulin sensitivity.

Visceral fat, waist circumference, and BMI: impact of race/ethnicity.

OBJECTIVE: BMI and waist circumference are used to define risk from excess body fat. Limited data in women suggest that there may be racial/ethnic differences in visceral adipose tissue (VAT) at a given BMI or waist circumference. This study tested the hypothesis that racial/ethnic differences exist in both men and women in the relationship of anthropometric measures of body composition and computed tomography (CT)-determined VAT or subcutaneous adipose tissue (SAT). METHODS AND PROCEDURES: Subjects included 66 African American, 72 Hispanic, and 47 white men and women, aged > or =45. Waist circumference and BMI were measured using standard methods. Total abdominal and L4L5 VAT and SAT were measured using CT. RESULTS: Among both men and women, groups did not differ in waist circumference or BMI. White men had greater L4L5 VAT than African-American men, and both white and Hispanic men had greater total VAT than African-American men. Among women, Hispanics and whites had greater L4L5 VAT than African Americans, and Hispanics had greater total VAT than African Americans. The slope of the linear relationship between BMI or waist circumference and VAT was lower in African Americans than in Hispanics and/or whites. DISCUSSION: Middle-aged and older African-American men and women had lower VAT despite similar BMI and waist circumference measurements. Altered relationships between anthropometric measures and VAT may have implications for defining metabolic risk in different populations. Different waist circumference or BMI cutoff points may be necessary to adequately reflect risk in different racial/ethnic groups.

Influence of BMI and gender on postprandial hormone responses.

OBJECTIVE: Influences of gender and body weight on the hormonal response to eating are not well understood. This study was conducted to determine a convenient time-point to evaluate peak postprandial hormone responses and to test the hypothesis that gender and BMI interact to produce differences in postprandial secretion of selected humoral markers implicated in hunger and satiety. RESEARCH METHODS AND PROCEDURES: Fasting blood glucose, insulin, leptin, ghrelin, glucagon-like peptide-1, and glucagon were measured in normal-weight (20 or= 30 kg/m2) men (n = 9) and women (n = 11). A standard liquid meal was consumed, and humoral measurements were repeated every 10 minutes for 1 hour. Data were analyzed using repeated measures ANOVA with BMI and gender as main effects. RESULTS: Obese subjects had delayed peak insulin responses (p = 0.004), whereas obese men had a delayed nadir ghrelin response (p = 0.05). Obese subjects had higher and more sustained postprandial glucose (p = 0.02), and greater fasting (p = 0.0004) and postprandial insulin (p = 0.0001). Ghrelin decreased after the meal (p = 0.003); the percent change from fasting tended to be reduced in obese subjects (p = 0.07). Men had greater fasting (p = 0.02) and postprandial (p = 0.03) glucagon and a subtle postprandial decline in plasma leptin (p = 0.01). DISCUSSION: Peak hormone responses occurred 20 to 40 minutes after eating. Measurements made during this interval may be useful in evaluating postprandial response magnitude. Peak/nadir responses and time courses of postprandial responses are influenced by gender and BMI. Nutritional studies need to account for variability introduced by these factors.

Cardiovascular function in a rat model of diet-induced obesity.

The obesity-prone/obesity-resistant rat model has been used to study mechanisms responsible for obesity-related abnormalities in renal function and blood pressure, but whether this model exhibits cardiac dysfunction has not been determined. We tested the hypothesis that obesity-prone rats would display cardiovascular abnormalities seen in other diet-induced obese models (ie, hypertension, tachycardia, left ventricular hypertrophy, increased collagen deposition, reduced cardiac contractility, and increased end diastolic pressure). Male Sprague-Dawley rats were fed a control diet or a moderate fat diet containing 32% kcal as fat while hemodynamics were continuously monitored using telemetry. After 12 weeks, obesity-prone rats were significantly heavier and had greater body fat compared with obesity-resistant rats and controls, but daily (20 hours/d) averages and diurnal rhythms of blood pressure and heart rate did not differ among groups. Echocardiographic indices of cardiac structure and function, histological evidence of cardiac collagen, and directly measured heart weights did not differ among groups. Peak left ventricular pressure, end diastolic pressure, +dP/dt, and -dP/dt were also not significantly different among groups. Plasma cholesterol and hepatic cholesterol were significantly higher in obesity-prone rats compared with obesity-resistant rats and controls; hepatic triglycerides were higher in obesity-prone rats compared with controls (P< or =0.05). Leptin was significantly higher in obesity-prone rats compared with controls and across all groups was significantly correlated with body fat (P< or =0.05). These results suggest that 12 weeks of a moderate fat diet in the obesity-prone/obesity-resistant rat model induced lipid and endocrine abnormalities typical of obesity but was not sufficient to cause significant cardiac abnormalities.

Loss of diurnal rhythms of blood pressure and heart rate caused by high-fat feeding.

BACKGROUND: Diet-induced obesity using ad libitum high-fat feeding in rabbits causes losses in diurnal rhythms of blood pressure (BP) and heart rate (HR). Because obesity is associated with hypertension, it is difficult to determine independent effects of ad libitum feeding and obesity in altering diurnal rhythms. We studied diurnal rhythms of BP and HR after controlling BP during obesity development using hydralazine. METHODS: New Zealand white rabbits were divided into lean control (LC), lean hydralazine-treated (LH), obese control (OC), and obese hydralazine-treated (OH) groups. Lean animals consumed a maintenance diet, whereas obese animals consumed an ad libitum high-fat diet. Over 12 weeks, BP and HR were monitored from 11:00 to 07:00 using telemetry. Hydralazine treatment consisted of 6 mg/kg/day and 10 to 14 mg/kg/day for LH and OH, respectively. Diurnal rhythms were evaluated using day-night values (day, 11:00 to 16:00 average; night, 02:00 to 07:00 average). RESULTS: Compared with control values, diurnal HR rhythm was abolished on day 1 of high-fat feeding (61.4 +/- 3.6 v 3.1 +/- 4.2 beats/min, respectively; P

Extracellular matrix remodeling in the heart of the homocysteinemic obese rabbit.

Despite the strides made toward understanding cardiac abnormalities in obesity-induced hypertension, the composition and concentration of cardiac extracellular matrix (ECM) components resulting from diet-induced obesity are largely unknown. Previous studies from our laboratory have demonstrated differential expression of collagens, growth factors, and homocysteine (Hcy) in pressure overload models of cardiac hypertrophy. The hypothesis of the present study was that left ventricular hypertrophy (LVH) from the combined pressure and volume overload of obesity induced cardiac fibrosis in part by increasing Hcy, increasing transforming growth factor-beta1 (TGF-beta1), and decreasing decorin. Using the rabbit model, we examined the changes in cardiac collagen accumulation, plasma Hcy, left ventricular (LV) TGF-beta1, and LV decorin after 12 weeks of developing obesity. Cardiac fibrosis was analyzed by trichrome stain for collagens. Total collagens types I and III, TGF-beta1, and decorin were analyzed in tissue homogenates by immunoblots and quantitated with a densitometer. After 12 weeks, rabbits eating a high-fat diet had greater body weight (5.38 +/- 0.3 kg v 3.73 +/- 0.6 kg) and greater LV weight (5.08 +/- 0.05 g v 3.86 +/- 0.17 g) compared with lean rabbits. Heart rate was also significantly higher in obese than in lean rabbits (221 +/- 8 v 173 +/- 5 beats/min). Plasma concentrations of circulating Hcy were 16.9 +/- 2.4 micromol/L and 24.3 +/- 1.8 micromol/L in lean and obese rabbits, respectively. Compared with lean rabbits, obese rabbits had increased interstitial and perivascular collagen, a 4-fold increase in the medial/lumen ratio of coronary vessels, a 1.75-fold increase in cardiac collagen I, and a 1.5-fold increase in cardiac collagen III levels. Levels of TGF-beta1 were increased 1.75-fold, whereas decorin levels were significantly reduced in obese compared with lean rabbits. In conclusion, a high-fat diet, even over a period as short as 12 weeks, causes fibrosis in coronary vessels as well as accumulation of collagen in the cardiac interstitium. The accumulation of cardiac collagen was associated with induction of Hcy and TGF-beta1 and with suppression of decorin.

A comparison of two exercise training programs on cardiac responsiveness to beta-stimulation in obesity.

We demonstrated previously that exercise training did not restore normal cardiac beta-adrenergic responsiveness in obese rabbits. This study tested the hypothesis that an increased training volume was required to attenuate obesity-related reductions in isolated heart responsiveness to isoproterenol. Female New Zealand White rabbits were divided into lean control, lean exercise-trained, obese control, and obese exercise-trained groups. For the exercise-trained groups, total treadmill work over 12 weeks was increased 27% when compared with lean and obese animals trained with lower total training volume. After 12 weeks, Langendorff isolated hearts were used to study developed pressure, +dP/dt(max), and -dP/dt(max) responses to isoproterenol (10(-9) - 3 x 10(-7) M). Concentration-response data were fit to a sigmoidal function using a four-parameter logistic equation. Controls were compared with animals trained under the low- and high-training volume programs using one-way analysis of variance and Tukey's post-hoc test; separate analyses were conducted for lean and obese rabbits. In both lean and obese groups trained under the high-training volume program, EC50 values for +dP/day(tmax) and -dP/dt(max) were higher compared with same-weight controls and animals trained under the low-training volume program, indicating that contractility and relaxation responsiveness to isoproterenol was reduced by the higher training volume. Therefore, these data indicate that increased training volume failed to attenuate obesity-related decrements in isolated heart responsiveness to beta-adrenergic stimulation and caused reduced sensitivity to isoproterenol in both lean and obese animals.

Hydralazine treatment alters body composition in the rabbit model of obesity.

AIMS: While hydralazine is commonly used as monotherapy in animal studies, its potential side effects are seldom acknowledged. Purported side effects occur from sympathetic and renin-angiotensin system activation, and include tachycardia, oedema, and nausea. We hypothesized that these side effects would alter body composition by increasing body water and/or decreasing body fat. METHODS: Female New Zealand White rabbits were divided into lean and obese control and hydralazine-treated groups. Lean rabbits ate a maintenance diet for 12 weeks; obese rabbits ate an ad lib high fat diet. Hydralazine was administered at 6 and 10-14 mg kg(-1) day(-1) for lean and obese hydralazine groups, respectively. Body composition was determined using triplicate 2-3 g samples of whole body homogenate, and analysed using 2 x 2 ANOVA for diet vs. hydralazine effects. RESULTS: Hydralazine-treated animals had lower body fat (15.7 +/- 1.1 and 21.8 +/- 1.0%, respectively) and higher body water (59.8 +/- 0.8 and 55.4 +/- 0.6%, respectively) compared with controls. While obese controls were heavier than obese hydralazine-treated animals (5.12 +/- 0.09 vs. 4.73 +/- 0.11 kg, respectively) and had greater overall feed consumption (13.5 +/- 0.4 vs. 11.8 +/- 0.4 kg, respectively), a subsequent analysis using subsets that did not differ in body weight or feed consumption yielded the same conclusions. Plasma adrenaline and noradrenaline did not differ between control and hydralazine-treated groups. CONCLUSIONS: Use of hydralazine to control blood pressure alters body composition. Direct or indirect effects of hydralazine may impact physiological systems under study. Alterations in adipose tissue may be of particular concern because of its endocrine function.

Isolated heart responsiveness to beta-simulation after exercise training in obesity.

PURPOSE: Exercise training results in many health benefits, but few studies have focused on whether exercise training might attenuate the adverse effects of obesity on heart function. Therefore, the purpose of this study was to determine whether exercise training attenuated obesity-related decreases in systolic contractile function in response to beta-adrenergic stimulation, using the rabbit model of obesity. METHODS: Female New Zealand white rabbits were divided into four groups: lean sedentary, lean exercise-trained, obese sedentary, and obese exercise-trained. Obese rabbits were fed an ad libitum high-fat diet. Exercise-trained rabbits underwent a 12-wk progressive treadmill exercise training protocol. After 12 wk, the Langendorff isolated heart method was used to study developed pressure, +dP/dt, and -dP/dt responses to increasing concentrations of isoproterenol (10(-9)--3 x 10(-7) M). Log concentration-response data were fit to a sigmoidal function, using a four-parameter (minimum, maximum, EC(50), slope) logistic equation. Groups were compared using a 2 x 2 analysis of variance. RESULTS: Although obesity shifted the concentration-response curves for developed pressure, +dP/dt, and -dP/dt to the right as indicated by an increase in the EC(50) (P < or = 0.05), there was no effect of exercise training on any of the logistic regression parameters. EC(50) (log M) values for combined lean versus combined obese were -8.50 +/- 0.7 vs -8.20 +/- 0.09 (developed pressure), -8.04 +/- 0.06 vs -7.68 +/- 0.07 (+dP/dt), and -8.17 +/- 0.07 vs -7.91 +/- 0.09 (-dP/dt). CONCLUSION: These results confirm the negative effect of obesity on responsiveness of the isolated heart to beta-adrenergic stimulation but indicate that exercise training does not significantly attenuate obesity-related changes.

Exercise training in obesity lowers blood pressure independent of weight change.

PURPOSE: We used the rabbit model of obesity and exercise training to determine effects of exercise training during the development of obesity on resting blood pressure and heart rate, ventricular hypertrophy, blood volume, and hormonal profile. METHODS: Female New Zealand white rabbits were assigned to one of four groups: lean sedentary (L-S, N = 17), lean exercise-trained (L-EX, N = 16), obese sedentary (O-S, N = 18), and obese exercise-trained (O-EX, N = 15). Lean rabbits were fed a maintenance diet whereas obese rabbits were fed an ad libitum high fat (10% added fat) diet. Simultaneously, exercise-trained animals underwent a progressive treadmill exercise training protocol for 12 wk. After 12 wk of diet and exercise regimens, resting blood pressure and heart rate were measured from a central ear artery catheter. Ventricular hypertrophy was evaluated using wet ventricular weights. Blood volume was measured using the Evans blue dye procedure; hormonal profile was evaluated from arterial plasma/serum samples. RESULTS: After 12 wk, O-S and O-EX had similar body weights and similar percentage increases in body weight. Despite similar body weights, O-EX had an approximate 6-mm Hg lower mean blood pressure compared with the elevated pressure seen in O-S (P < or = 0.05). Obese rabbits had greater resting heart rate, plasma cholesterol and triglycerides, and plasma renin activity compared with lean rabbits, and these values were unaffected by exercise training. Plasma and blood volumes, as well as plasma insulin, cortisol, and aldosterone were unaffected by exercise training. CONCLUSION: These data suggest that exercise training, in the absence of differences in body weight, may be useful in the reduction of obesity-induced hypertension but that other therapies may be needed in order to control other cardiovascular risk factors.