Effects of short-term hypocaloric diet on sympatho-vagal interaction assessed by spectral analysis of heart rate and blood pressure variability during stress tests in obese hypertensive patients.

We examined the effects of a short-term low-calorie diet on the activity of the autonomic nervous system during stress tests in obese patients with hypertension by analysis of heart rate and blood pressure variability. Eighteen obese inpatients with essential hypertension were given a regular-calorie diet (1,600 kcal, NaCl 7 g) for 4 days, and then a low-calorie diet (1,100 kcal, NaCl 7 g) for 11 days. During both the regular-calorie diet and low-calorie diet, power spectral analysis of heart rate and blood pressure variability at rest and during mental arithmetic test, deep breathing test, isometric handgrip test or cold pressor test was performed. Body weight and 24-h ambulatory blood pressure were significantly lower during the low-calorie diet than during the regular-calorie diet. Systolic and diastolic blood pressure significantly increased over the handgrip test and cold pressor test during both diets. The low frequency component (LF) of systolic blood pressure, a marker of sympathetic activity to the vasculature, during the deep breathing test and cold pressor test were significantly lower on the low-calorie diet than the regular-calorie diet. The blood leptin concentration was also significantly lower on the low-calorie diet than the regular-calorie diet. The decrease in body weight was positively correlated with the decrease in blood leptin concentration. The LF/high frequency component (HF) ratio of the RR interval at rest on the regular-calorie diet was negatively correlated with the decrease in blood leptin concentration. These results suggest that the autonomic nervous function assessed by analysis of heart rate and blood pressure variability during stress tests may be improved by weight loss due to a short-term low-calorie diet in obese patients with hypertension.     

The effects of weight reduction on blood pressure in 301 obese patients

The effects of weight reduction on blood pressure were assessed in 301 obese patients. Weight reduction was achieved by behavior modification, medication, or their combination and was associated with significant reductions in systolic and diastolic blood pressure. The weight reduction method was less important than the amount of weight lost in determining reductions in blood pressure. The greatest reductions in weight and blood pressure occurred during the first half of weight loss, suggesting that even brief treatment (ie, 8 to 10 weeks) may benefit obese, hypertensive patients. Despite repeated measurements, 36 patients who failed to lose weight showed no decrease in blood pressure. Although blood pressure rose during follow-up in patients who regained weight, it remained below baseline levels. These findings provide further support for weight reduction in the control of hypertension.     

Mechanisms in obesity-related hypertension: role of insulin and catecholamines

Although the association of obesity and hypertension is well recognized, the mechanisms involved in the pathogenesis of increased blood pressure in the obese are poorly understood. Recent studies addressing the impact of 1) body fat distribution on blood pressure and 2) dietary intake on sympathetic nervous system (SNS) activity suggest a plausible hypothesis that relates the hypertension of the obese to hyperinsulinemia and SNS stimulation. Hypertension in the obese is associated with fat accumulation in the upper body segments; this type of obesity is also characterized by hyperinsulinemia and insulin resistance. Insulin, moreover, is an important signal in the relationship between dietary intake and SNS activity: increased insulin levels are associated with SNS stimulation. The hyperinsulinemia of obesity may, therefore, increase blood pressure by 1) direct effects of insulin to stimulate renal sodium reabsorption, and 2) sympathetic stimulation of the heart, blood vessels, and kidney. Conversely, SNS suppression and diminished insulin following caloric restriction may explain the hypotensive effects of caloric restriction in obese hypertensive subjects. The hypothesis presented here emphasizes the important role of diet in the treatment of obese hypertensive subjects. The efficacy of caloric restriction, weight loss, and exercise in reducing blood pressure in the obese is linked to diminished insulin and SNS activity and may be viewed as evidence in favor of this hypothesis.     

Diagnosis and management of hypertension in obesity

Cardiovascular risk in a patient with obesity hypertension increases with the extent of risk factor clustering. It is therefore important to determine the global risk of a patient with hypertension rather than to focus solely on blood pressure. Every hypertensive should be screened for other than blood pressure risk factors, target organ damage and concomitant diseases or accompanying clinical conditions. Assessment of blood pressure and target organ damage might be more difficult in obese hypertensives than in normal-weight patients. Intensive lifestyle interventions can reduce weight, and decrease blood pressure and cardiovascular risk in obese hypertensive patients. Current guidelines do not provide specific recommendation for pharmacological management of the hypertensive patients with obesity. Recent trials have consistently shown that therapy involving beta-blockers and diuretics may induce more new-onset diabetes compared with other combination therapies. Several lines of evidence suggest that anti-hypertensive agents that block the renin-angiotensin system may be especially beneficial in treating obese hypertensive patients. Hypertension management in obese individuals is complicated by poorer response to treatment, and the increased need for multiple medications. It is important to consider obstructive sleep apnoea in the differential diagnosis of hypertensive patients who respond poorly to combination therapy with anti-hypertensive medications.     

Management of hypertension in overweight and obese patients: A practical guide for clinicians

The association between obesity and cardiovascular disease is well established, and up to 60% of overweight or obese patients have hypertension. Dietary interventions associated with modest weight loss are effective in controlling blood pressure and in reducing use of antihypertensive drug therapy in overweight and obese patients. However, long-term maintenance of weight loss is achieved only in a small proportion of patients. Orlistat and sibutramine may help to achieve and maintain weight loss but may not be sufficient to control blood pressure in overweight and obese hypertensive patients. Consequently, antihypertensive drug therapy is often necessary in addition to weight loss interventions. Few studies have investigated different antihypertensive drugs, specifically in overweight and obese patients with hypertension. Based on studies involving obese and nonobese patients, first-line treatment options include a diuretic alone or an angiotensin-converting enzyme (ACE) inhibitor alone. If monotherapy is inadequate for blood pressure control, combination therapy with diuretic and ACE inhibitor and/or combining either of these drugs with a calcium channel blocker are reasonable treatment options. Additional studies to further clarify the management of these patients are warranted.     

Abstracts

The relationship of body fat distribution with blood pressure, fat cell weight and extracellular fluid volume was studied and compared in 20 obese hypertensive men and 20 obese hypertensive women of similar age, degree of overweight and blood pressure level. Body fat distribution, as reflected by the ratio between waist and hip circumference (W/H ratio), was significantly higher in male than in female obese patients. The W/H ratio was positively and independently correlated with systolic arterial pressure both in males and females. However, for the same W/H ratio, systolic arterial pressure was higher in females. The W/H ratio was positively correlated with gluteal fat cell weight only in males and not in females. Both in males and females, the W/H ratio was positively correlated with extracellular fluid volume, independently of the level of blood pressure level and/or the degree of obesity. The study provided evidence that the relationship between body weight and blood pressure in obese hypertensives is affected by the sex-dependence of body fat distribution with possible interferences on fat cell weight and extracellular fluid volume.

Several epidemiological studies have emphasized the positive correlation observed between body weight and blood pressure in man (1-4). Many investigations have documented the association of blood pressure with body weight, weight to height, overweight or other indices of fatness such as skinfold thickness (1-6). However, the correlation coefficients of these different relationships were found constantly small, indicating that the relationship between overweight and blood pressure is somewhat complex.

In patients with hypertension, body weight was shown to be strongly related with the levels of both blood pressure and extracellular fluid volume (7-9). On the other hand, patients with overweight and hypertension were found to be principally affected by hypertrophic obesity, as shown by the evaluation of fat cell weight (10). However these findings were exclusively observed in males. No solid data were reported in females.

The relationships between body weight and extracellular fluid on one hand, and between body weight and fat cell weight on the other hand, are certainly different in males and in females. First, in females, extracellular fluid volume is submitted to cyclic changes in sodium balance involving the effect of sex steroid hormones (1, 7, 11). Second, body fat distribution, a parameter which is weakly correlated to blood pressure (2, 11, 12), is different in males and females. In males, body fat predominates in the upper part of the body while, in females, adiposity is mainly observed in the lower part of the body (5). In that regards, it is important to investigate body fat distribution in males and females with obesity and hypertension, with reference to the most important parameters involved in body weight composition : fat cell weight and extracellular fluid volume.     

Effect of biliopancreatic diversion on hypertension in severely obese patients.

Hypertension is a medical disorder frequently associated with severe obesity, and the effect of weight loss on the reduction of blood pressure has been well established. In this study, the relationships between the weight loss surgically obtained by biliopancreatic diversion and blood pressure were investigated in a population of severely obese patients with preoperative hypertension. At 1 year following the operation, blood pressure was normalized in more than half of patients; in a further 10% of cases the hypertensive status resolved within the 3-year follow-up period. The resolution of hypertension was independently associated with age and body weight and was unrelated to sex, the amount of weight loss, or body fat distribution. In severely obese patients with hypertension undergoing bariatric surgery, biliopancreatic diversion is advisable since it achieves and supports the maintenance of body weight close to the ideal value.     

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension

Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved.     

Effects of weight loss on body composition and pulmonary function.

BACKGROUND: The relationship between obesity, impaired respiratory function and weight loss is established. OBJECTIVE: Some aspects need further elucidation: the different impact of the pathological modifications of body compartments (total and regional fat mass and lean body mass) on respiratory function, the choice of a restricted diet, the relationship between the modifications of body compartments and the variations in respiratory parameters after weight loss. METHODS: The restricted diet was elaborated according to the traditional Mediterranean diet. In a series of 16 obese patients, respiratory function was assessed by spirometry; body composition was assessed by dual-energy X-ray absorptiometry, allowing the direct estimation of total and segmental body fat and lean body mass. RESULTS: Weight loss was sustained mainly by fat mass decrease, mostly upper body fat. Total and truncal lean body mass were not affected. Lung volumes and function were improved. A correlation was observed between lean body mass and respiratory parameters, and was unmodified after weight loss. CONCLUSIONS: Mediterranean-style restricted diet was well accepted and enabled a selective decrease in fat mass, with a good improvement in lung function. Truncal fat (as well as abdominal fat) was decreased, while truncal lean body mass (i.e. respiratory muscles) were not affected, as expected in obese subjects with respiration problems.     

A Moderately High Fat Diet Promotes Salt-Sensitive Hypertension in Obese Zucker Rats by Impairing Nitric Oxide Production

The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO_x) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO_x excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO_x excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge.     

Relationship among systolic blood pressure, serum insulin and leptin, and visceral fat accumulation in obese children.

The aim of this study was to clarify the relation among systolic blood pressure (SBP), serum insulin, leptin, visceral fat accumulation and family history of hypertension, and to elucidate the pathophysiologic mechanism of blood pressure elevation in obese children. This study examined 109 obese children with a family history of hypertension (OF: 77 boys and 32 girls), and 83 obese children without such a history (ON: 60 boys and 23 girls). Body height and weight, and percent of body fat were measured and the percent of relative weight was calculated. Both boys and girls, the two groups were matched with respect to age, height, and weight. SBP was measured in the seated position using an automated recorder. Abdominal fat thickness (maximum preperitoneal fat thickness: Pmax; minimum subcutaneous fat thickness: Smin) were measured using ultrasonography. The fasting serum levels of insulin and leptin were measured by radioimmunoassay. All subjects were simply obese, without diabetic states. In both OF and ON, SBP was associated with insulin levels, leptin levels, and Pmax by simple regression analysis, and with insulin levels by stepwise regression analysis. Insulin levels were associated with leptin levels and Pmax by simple regression analysis, and with leptin levels by stepwise regression analysis. These findings indicated that SBP was associated with hyperinsulinemia, hyperleptinemia and visceral accumulation regardless of a family history of hypertension in obese children, as well as later in adult obesity. For primary prevention of hypertension, these results support the importance of implementation of a strategy to prevent obesity, especially visceral obesity. An effective strategy for preventing childhood obesity will contribute to a future decrement in cases of metabolic syndrome, including adulthood hypertension.     

Obesity and hypertension

Substantial evidence from epidemiological data supports a link between obesity and hypertension. However, the relationship between the two disorders is not straightforward and most likely represents an interaction of demographic, genetic, hormonal, renal, and hemodynamic factors. Age, race, and sex also modulate the strength of the association between obesity and hypertension. Hyperinsulinemia, which is characteristic of obesity, can contribute to the probability of developing hypertension by activating the sympathetic nervous system (SNS) and by causing sodium retention. The pressor effect of insulin in obesity may be further enhanced by the observation that its vasodilator action can be blunted in obese subjects. Preliminary data have shown that leptin, whose levels are increased in most obese individuals, can contribute to hypertension in obesity through its effects on insulin, SNS, and sodium excretion. The kidney may also have a role in the pathophysiology of hypertension in obesity. Abnormal renal sodium handling coupled with structural changes in the kidney of an obese patient can raise blood pressure. In addition, obesity is associated with distinct cardiovascular hemodynamic alterations and development of eccentric myocardial hypertrophy. Most of these obesity-associated abnormalities, as well as hypertension itself, can be reversed by weight loss. Furthermore, weight loss can prevent, or at least delay, the development of hypertension in patients with high-normal blood pressure. Weight reduction should be the first-line treatment in every obese hypertensive patient. However, the majority of patients will need pharmacologic intervention in conjunction with weight loss. Selection of antihypertensive agents in the overweight patient should take into account the mechanisms leading to hypertension and the metabolic abnormalities that characterize the obese patient.     

Hypertension and obstructive sleep apnea

Obstructive sleep apnea is a common disorder that is often unrecognized and underappreciated. Emerging evidence suggests that there is a causal link between obstructive sleep apnea and hypertension. This relationship appears to be independent of other comorbidities that have been previously linked to hypertension, such as obesity. The majority of studies support the contention that alleviation of sleep disordered breathing has a clinically significant beneficial impact on decreasing both nighttime and daytime blood pressure. A pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension is not fully elucidated. However, there is consistent evidence that autonomic mechanisms are implicated. Sympathetic activation along with humoral responses to repetitive episodes of hypoxemia and apnea over the longer term may cause vasoconstriction, endothelial dysfunction, and possibly hypertension. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to hypertension in this patient population.     

A moderately high fat diet promotes salt-sensitive hypertension in obese zucker rats by impairing nitric oxide production

The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO(x)) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO(x) excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO(x) excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge.     

The respiratory muscles in eucapnic obesity: Their role in dyspnea

Regular exercise appears to be one of the best predictors of successful weight maintenance. Although physical activity and exercise are important components in the prevention and treatment of obesity, many obese adults without coexisting disorders are unable to exercise due to dyspnea on exertion. As a result they may not participate in regular physical activity. Therefore exertional dyspnea in obese adults is also an obstacle to the prevention and treatment of obesity and coexisting comorbidities. The available data suggest that increased respiratory muscle force generation, and the concomitant increase in respiratory neural drive associated with increased ventilation are an important source of sensation of respiratory effort in obese subjects. Whether activity-related breathlessness is due to either abnormal respiratory mechanical factors (flow limitation and/or chest elastic loading) or the increased metabolic demand of locomotion in obesity, or both of these together, the available data indicate that intensity of dyspnea at any given ventilation and oxygen uptake does not increase in obese subjects as compared with normal weight control subjects. Does this mean that respiratory mechanical factors are unlikely to be contributory? Nonetheless, the component of metabolic cost of breathing may not be accounted for in the measured mechanical work of breathing because of the number of included complex variables. That a decrease in efficiency of the respiratory muscles during exercise contributes to dyspnea in hyperinflating obese subjects should not be disregarded.     

Obesity hypoventilation syndrome: mechanisms and management

Obesity hypoventilation syndrome describes the association between obesity and the development of chronic daytime alveolar hypoventilation. This syndrome arises from a complex interaction between sleep-disordered breathing, diminished respiratory drive, and obesity-related respiratory impairment, and is associated with significant morbidity and mortality. Therapy directed toward reversing these abnormalities leads to improved daytime breathing, with available treatment options including positive pressure therapy, weight loss, and pharmacological management. However, a lack of large-scale, well-designed studies evaluating these various therapies has limited the development of evidence-based treatment recommendations. Although treatment directed toward improving sleep-disordered breathing is usually effective, not all patients tolerate mask ventilation and awake hypercapnia may persist despite effective use. In the longer term, weight loss is desirable, but data on the success and sustainability of this approach in obesity hypoventilation are lacking. The review outlines the major mechanisms believed to underlie the development of hypoventilation in this subgroup of obese patients, their clinical presentation, and current therapy options.     

The effects of weight loss treatments on upper and lower body fat

The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may have comparable amounts of adipose tissue but remain relatively free from the metabolic consequences of obesity. This raises an obvious question-are there particular weight reducing treatments which specifically target intra-abdominal fat? In theory, surgical removal of upper body fat should be effective. In reality, neither liposuction nor apronectomy ('tummy tuck') have any beneficial metabolic effects, they simply remove subcutaneous adipose tissue which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass operations may be dramatically effective in improving blood pressure, insulin sensitivity and glucose tolerance. However, these benefits result from a parallel reduction in visceral and total body fat. Studies of body fat distribution in postmenopausal women confirm that the marked decrease in adiposity, following a programme of very low calorie diet and exercise, reflects a comparable reduction in visceral and thigh fat. The reduction in waist circumference after a low fat/exercise programme suggests a similar situation in men. Exercise has an important role in treatment but, once again, the fat loss is generalised. Nevertheless, the improved metabolic parameters seen in exercising obese subjects, independent of weight loss, suggest other beneficial actions. Growth hormone (GH) has a marked lipolytic action. GH replacement treatment for GH deficient adults with pronounced abdominal fat deposition, has been shown to reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal subcutaneous fat. Similar beneficial actions on abdominal fat have been reported following treatment with testosterone in obese men. The potential hazards of such treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective in reducing total body fat but the results from a six month randomised controlled trial indicates that it does not specifically influence changes in waist circumference associated with weight loss. In conclusion, any treatment which reduces total body fat will, by its nature, reduce intra-abdominal visceral fat. There are presently no specific treatments which can be recommended for intra-abdominal fat but increasing knowledge of the biochemical aberrations associated with visceral adiposity may lead to more specific therapies for the future.     

Obesity and cardiovascular disease

Obesity is a major contributor to the prevalence of cardiovascular disease in the developed world, and yet has only recently been afforded the same level of attention as other risk factors of coronary artery disease. Obesity is a chronic metabolic disorder associated with cardiovascular disease and increased morbidity and mortality. It is apparent that a variety of adaptations/alterations in cardiac structure and function occur as excessive adipose tissue accumulates, even in the absence of comorbidities. Shifts toward a less physically demanding lifestyle are observed today throughout different populations, and this scourge associated with obesity implicates a corresponding increase in the number of individuals afflicted with the metabolic syndrome, which defines the obese patient as being “at risk.” Adipose tissue is not simply a passive storehouse for fat, but an endocrine organ that is capable of synthesizing and releasing into the bloodstream a variety of molecules that may impact unfavorably the risk factor profile of a patient. Indeed, obesity may affect atherosclerosis through unrecognized variables and risk factors for coronary artery disease such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, and the prothrombotic state. By favorably modifying lipids, decreasing blood pressure, and decreasing levels of glycemia, proinflammatory cytokines, and adhesion molecules, weight loss may prevent the progression of atherosclerosis or the occurrence of acute coronary syndrome events in the obese high-risk population.     

Effects of long-term physical training on body fat, metabolism, and blood pressure in obesity.

Twenty-seven women with varying degrees of obesity were physically trained for 6 mo on an ad lib. diet. Body fat changes were positively correlated with the number of fat cells in adipose tissue. Obese women with fewer fat cells decreased in weight during training whereas women with severe obesity and an increased number of fat cells even gained weight. Blood pressure decreased consistently after training. Blood pressure elevation was not associated with body fat mass, nor was a decrease in blood pressure associated with a decrease in body fat or with pretraining blood pressure level. There were, instead, correlations between decreases in blood pressure on the one hand and initial concentrations and decreases in plasma insulin and triglycerides and blood glucose on the other. These results suggest an association between elevated blood pressure and metabolic variables. The possibility of treating and preventing early essential hypertension with methods that also correct the metabolic derangement, such as diet and exercise, should be given high priority in further research.     

Association between blood pressure and insulin resistance in obese females during weight loss and weight rebound phenomenon.

The purpose of this study was to investigate the effect of weight loss on blood pressure and its related variables in moderately obese Japanese females, including an investigation of the rebound phenomenon. Study I examined the effects of weight loss on blood pressure in 138 moderately obese, nondiabetic females (BMI 29.3+/-0.3 kg/M2; age, 46.3+/-0.8 years) during a 3-month therapeutic dietary and exercise program. Study II investigated the effect of weight rebound on blood pressure over an additional 21 months of exercise in 48 subjects from Study I subjects. After 3 months, the BMI significantly decreased to 27.9+/-0.3 kg/m2. Abdominal total fat, visceral fat (V), and subcutaneous fat (S) also decreased significantly. In addition, the summation of insulin (sigmaIRI), plasma glucose (sigmaPG) and HOMA during 75 g oral glucose tolerance test also all significantly decreased. Significant decreases in both the SBP and DBP were observed after the 3 month weight reduction program. Multiple regression analysis revealed that the reduction in SBP was significantly and positively associated with the reduction in log sigmaIRI and the reduction in log 24h-urinary norepinephrine excretion at the end of Study I. The DBP showed a significantly positive association with the log sigmaIRI. With regard to the weight rebound phenomenon, Study II showed that the SBP, DBP and sigmaIRI all increased significantly, and a positive correlation was observed between the changes in the SBP and those in the log sigmaIRI. However, no such correlation was observed regarding the abdominal total fat and visceral fat during both periods. These results suggest that weight loss therefore caused the BP to decrease due to both an improvement in hyperinsulinemia and a decrease in the adrenergic activity which may be involved in the urinary catecholamine. As a result, hyperinsulinemia is thus considered to play an important role in the pathogenesis of blood pressure due to obesity not only during weight loss, but also during the weight rebound phenomenon.